Alzheimer's & other dementias

Inflammation in Alzheimer's

Older news items (pre-2010) brought over from the old website

Evidence challenges inflammation theory for Alzheimer's

Although it has long been theorized that inflammation plays a role in the development of Alzheimer’s, repeated studies have failed to find consistent evidence that anti-inflammatory drugs are helpful. Now a brain tissue study reveals that supporting brain cells called microglia are not activated in the presence of tau tangles in the brains of Alzheimer’s patients, as has been predicted, and as would be the case if there were inflammation. Instead, microglia are degenerating. It’s suggested that it is this loss of microglia that contributes to the loss of neurons, and thus to the development of dementia. The next step is to find out why the microglia are dying.

Streit, W.J. et al. 2009. Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer’s disease. Acta Neuropathologica, Published online ahead of print.

Blood inflammation plays role in Alzheimer's disease

Data from the Framingham Heart Study has found that those with the highest amount of cytokines (protein messengers that trigger inflammation) in their blood were more than twice as likely to develop Alzheimer's disease as those with the lowest amount of cytokines, providing further evidence that inflammation plays a role in the development of Alzheimer's disease.

Tan, Z.S. et al. 2007. Inflammatory markers and the risk of Alzheimer disease: The Framingham Study. Neurology, 68, 1902-1908.

Alzheimer's disease linked to early inflammation

A new study of dementia in identical twins suggests that exposure to inflammation early in life quadruples one's risk of developing Alzheimer's disease. The study involved sifting the 20,000 participants in the Swedish Twin Registry for the 109 "discordant" pairs where only one twin had been diagnosed with dementia. Answers to health questions in the survey enabled the researchers to build a crude indicator of periodontal disease, measured indirectly by teeth lost or loose. Because this is not a direct measure of inflammation, the results need to be confirmed, but they do suggest that an inflammatory burden early in life, as represented by chronic gum disease, may have severe consequences later. The study also found that mental activities at age 40 did not seem to lower the risk of developing Alzheimer's, and the level of education was not a large factor once genes were taken into account (nevertheless, those with less high school and college education had 1.6 times the risk of dementia). Previous studies have shown that Alzheimer's is strongly genetic: If one twin has the disease, his or her identical twin has a 60% chance of developing it.

The study was presented at the first Alzheimer's Association International Conference on Prevention of Dementia, to be held June 18-21 in Washington, D.C.

Antibody detection in Alzheimer's may improve diagnosis, treatment

A study has found that people with Alzheimer’s disease have three to four times more antibodies to RAGE (receptor for advanced glycation end products) and beta amyloid — both major players in Alzheimer’s — than their healthy counterparts. The ability to measure these specific antibody levels could lead to a method for very early diagnosis. The finding may also point to a new treatment approach. The study supports the theory that autoimmunity and resulting inflammation play a big role in Alzheimer’s.

Mruthinti, S., Buccafusco, J.J., Hill, W.D., Waller, J.L., Jackson, T.W., Zamrini, E.Y. & Schade, R.F. 2004. Autoimmunity in Alzheimer’s disease: increased levels of circulating IgGs binding Ab and RAGE peptides. Neurobiology of Aging, 25 (8), 1023-1032.

A new hypothesis about Alzheimer's

A new theory about the cause of Alzheimer's disease has been proposed. According to this theory, Alzheimer’s arises as a consequence of inflammation, which creates abnormal metabolites out of normal brain molecules. These abnormal metabolites then modify "amyloid beta" proteins in the brain and cause them to misfold, thus accumulating into the fibrils and plaques characteristic of the disease. The inflammation process that creates these metabolites can be triggered by numerous stimuli, including infections that precede the onset of Alzheimer's disease by a significant amount of time — perhaps years. Traumatic head injuries, for example, are a major risk factor for later developing Alzheimer's disease. Inflammation is increasingly seen as playing a role in neurodegenerative diseases.

Zhang, Q., Powers, E.T., Nieva, J., Huff, M.E., Dendle, M.A., Bieschke, J., Glabe, C.G., Eschenmoser, A., Wentworth, P.Jr., Lerner, R.A. & Kelly, J.W. 2004. Metabolite-initiated protein misfolding may trigger Alzheimer's disease. Proceedings of the National Academy of Sciences, 101 (14), 4752-7.

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Cell Death

Older news items (pre-2010) brought over from the old website

Study links Alzheimer's disease to abnormal cell division

Neurons affected by Alzheimer’s and many other neurodegenerative diseases often start to divide before they die. A new mouse study shows that this abnormal cell division starts long before amyloid plaques or other markers of the disease appear, suggesting a new approach to therapy for Alzheimer's. The findings also shed new light on the theory that the accumulation of amyloid beta in the brain causes the neuron death in Alzheimer’s, indicating that micro-molecular aggregates (tiny clumps made up of several amyloid beta molecules) rather than amyloid plaques may trigger the disease.

Yang, Y., Varvel, N.H., Lamb, B.T. & Herrup, K. 2006. Ectopic cell cycle events link human Alzheimer's disease and APP transgenic mouse models. The Journal of Neuroscience, 26 (3), 775-784.

Abnormal cell division possible precursor of Alzheimer's

A study of genetically engineered mice sheds more light on the causes of Alzheimer’s. The study looked at what the reasons for neuron death apart from neurofibrillary tangles; they found an abnormal type of cell division occurring in tau proteins that may activate a cascade of abnormal events.

Andorfer, C., Acker, C.M., Kress, Y., Hof, P.R., Duff, K. & Davies, P. 2005. Cell-Cycle Reentry and Cell Death in Transgenic Mice Expressing Nonmutant Human Tau Isoforms. Journal of Neuroscience, 25, 5446-5454.

Nerve cell death in Alzheimer's is caused by a failed attempt at cell division

Researchers have uncovered a key piece of missing evidence in the proof that nerve cell death in Alzheimer's disease is caused by a failed attempt at cell division. They have found a significant number of brain cells in Alzheimer's patients with extra copies of chromosomes, showing attempts at cell division in cells that are not supposed to divide. This effort to divide may be the cause of the nerve degeneration and dementia in Alzheimer's disease. "It's almost as if Alzheimer's disease were a novel form of cancer." Cancer is characterized by uncontrolled cell division. In this study, scientists found uncontrolled cell division, arrested in the midst of the process, is the likely cause of the nerve cell destruction. It is speculated that the plaques which are a hallmark of Alzheimer's disease brain cells trigger an inflammatory response in the brain, and that this response brings with it proteins that trigger cell division. This finding may signal a new approach to the treatment of Alzheimer's, trying to prevent signals for the inflammatory response from reaching the cells or to prevent the cells from responding to the signals to divide.

Yang, Y., Geldmacher, D. S., & Herrup, K. (2001). DNA Replication Precedes Neuronal Cell Death in Alzheimer’s Disease. The Journal of Neuroscience, 21(8), 2661–2668. Retrieved from

Overproduction of the brain chemical galanin might contribute to cognitive decline

Overproduction of the brain chemical galanin during the early stages of Alzheimer’s may have an negative effect on the brain and contribute to the cognitive decline of patients, according to a study involving transgenic (mutated) mice. The study suggests the overproduction of galanin might be a response to the deterioration of brain cells ( people with Alzheimer's have twice as much galanin in certain areas of the brain as peers who die of something else). While initially galanin might be beneficial, as the disease progresses, the overexpression of galanin may become its own problem, contributing to cognitive decline. It seems that the memory loss that occurs with Alzheimer's may be caused by the combination of cell death and excess galanin. It may be that a drug that blocks galanin would slow or reverse the mental damage caused by the disease.

Steiner, R. A., Hohmann, J. G., Holmes, A., Wrenn, C. C., Cadd, G., Juréus, A., … Crawley, J. N. (2001). Galanin transgenic mice display cognitive and neurochemical deficits characteristic of Alzheimer’s disease. Proceedings of the National Academy of Sciences, 98(7), 4184–4189. doi:10.1073/pnas.061445598 .

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Amyloid-beta Proteins

Older news items (pre-2010) brought over from the old website

Why and how plaques form

Progress toward a drug that could actually stop Alzheimer’s

Amyloid plaques, characteristic of Alzheimer’s, are created when the amyloid precursor protein is cut into pieces incorrectly, which is governed by the γ-secretase complex. Acting on this complex is problematic however, as it is also involved in the regulation of a number of other essential proteins. New research with mouse models has now found that the complex assumes a different shape and function according to the tissue in which the secretase is active, and that they can specifically target the relevant variant, Aph1B γ-secretase, thus reducing formation of the plaques without any harmful side effects. The finding raises hopes for a drug that, for the first time, will succeed in stopping or even preventing Alzheimer's disease. However, many years of further research and development will be needed before such a drug will reach marketable status.

Serneels, L. et al. 2009. γ-Secretase Heterogeneity in the Aph1 Subunit: Relevance for Alzheimer's Disease. Science, Published Online March 19.

Paradoxical finding may shed new light on memory loss

Following a previous study, in which genetically engineered mice were prevented from getting Alzheimer’s by blocking a single site of cleavage of amyloid precursor protein (APP), studies of brain tissue from Alzheimer’s patients were found to have clearly more of this cleavage process than people of the same age who do not have the disease. However, much younger people without Alzheimer’s displayed as much as ten times the amount of the same cleavage event. The researchers now believe that normal memory loss is hyper-activated in Alzheimer’s, pointing to Alzheimer’s as a disorder affecting the plasticity, the ability to make and break memories, of the brain. Rather than the problem lying with the buildup of A-beta, the researchers suggest the problem lies in the downstream signaling of A-beta.

Banwait, S. et al. 2008. C-terminal cleavage of the amyloid-ß protein precursor at Asp664: a switch associated with Alzheimer's disease. Journal of Alzheimer’s Disease, 13 (1), 1-16.

Progression of Alzheimer's disease revealed

A new imaging agent is giving researchers information never before available about how and where Alzheimer’s progresses in the brain. Results suggest that amyloid plaques deposit sequentially, first appearing in the cingulate cortex/precuneus and frontal cortex areas, then progressing to the parietal and temporal cortex and caudate, and finally reaching the occipital cortex and sensory-motor cortex. These findings may explain why memory and judgment are often the brain functions first affected in Alzheimer's disease.

Klunk & Mathis 2005. Can In Vivo Amyloid Imaging with Pittsburgh Compound-B Tell Us Anything About the Time Course of Amyloid Deposition in Alzheimer's Disease. Paper presented at the 35th Annual Meeting of the Society for Neuroscience, Nov. 12-16, in Washington, D.C.

New light on how amyloid beta accumulation leads to long-term memory loss

A study using genetically engineered mice has shed new light on why the damage to brain tissue seen in Alzheimer’s leads to the loss of long-term memories. It seems that the accumulation of amyloid-beta peptides can deplete key proteins in the hippocampus, and this process can be worsened by increased activity of an enzyme called Fyn. The conversion of new information into long-term memories requires proteins (such as Arc and Fos) that help strengthen the synapses between specialized neurons in the hippocampus. Fyn is located at the synapses, where it regulates the activity of several memory-related proteins; increases in Fyn activity significantly increase the susceptibility of the hippocampal granule cells to the amyloid beta-induced depletion of memory proteins.

Palop, J.J., Chin, J., Bien-Ly, N., Massaro, C., Yeung, B.Z., Yu, G-Q. & Mucke, L. 2005. Vulnerability of Dentate Granule Cells to Disruption of Arc Expression in Human Amyloid Precursor Protein Transgenic Mice. Journal of Neuroscience, 25, 9686-9693.

Chin, J., Palop, J.J., Puoliväli, J., Massaro, C., Bien-Ly, N., Gerstein, H., Scearce-Levie, K., Masliah, E. & Mucke, L. 2005. Fyn Kinase Induces Synaptic and Cognitive Impairments in a Transgenic Mouse Model of Alzheimer's Disease. Journal of Neuroscience, 25, 9694-9703.

New light on why plaques form

Alzheimer's disease is characterized by an increasing deposit of the amyloid-β protein in the brain, which collect to form aggregations called 'plaques'. New research has unraveled how certain plaques are formed. It seems the plaques attach primarily to blood vessels, which show clear structural damage, leading to leakage between the blood vessels and the brain. Under normal circumstances, the blood vessels transport excess amyloid-β protein away from the brain. The findings suggest new treatment approaches.

Kumar-Singh, S., Pirici, D., McGowan, E., Serneels, S., Ceuterick, C., Hardy, J., Duff, K., Dickson, D. & Van Broeckhoven, C. 2005. Dense-Core Plaques in Tg2576 and PSAPP Mouse Models of Alzheimer’s Disease Are Centered on Vessel Walls. American Journal of Pathology, 167, 527-543.

Finding an Alzheimer's switch

One prominent theory of the cause of Alzheimer's involves the so-called "amyloid beta protein cascade," in which a protein called APP is clipped into shorter pieces by enzymes known as secretases. If the portion of APP clipped by the beta form of secretase is further clipped by a third form, gamma secretase, the resulting fragments are amyloid beta peptides, A-beta 40 and A-beta 42. A-beta 42 in particular is toxic and causes the formation of amyloid plaques. A new study has uncovered an unsuspected subunit of gamma-secretase, the protein CD147, which apparently regulates the production of the toxic peptides that cause amyloid plaques. CD147 is expressed in many tissues and has many functions besides its role in tumor invasion, including reproduction, inflammation, and protein transport and sorting within cells. It also has a role in neural function: when the CD147 gene is deleted in mice, the result is defective nervous system development, loss of working memory, spatial learning deficits, and disorientation — behaviors remarkably suggestive of Alzheimer's disease. Future research will attempt to uncover exactly how CD147 prevents excessive production of A-beta 42 peptides, and what causes it to fail.

Zhou, S., Zhou, H., Walian, P.J. & Jap, B.K. 2005. CD147 is a regulatory subunit of the ã-secretase complex in Alzheimer's disease amyloid â-peptide production. Proceedings of the National Academy of Sciences, Published online before print May 12, 2005, 10.1073/pnas.0502768102.

Beta amyloid accumulation shown to be trigger for onset of Alzheimer's

A study using genetically engineered mice has determined that early beta amyloid accumulation within neurons is the trigger for the onset of memory decline in Alzheimer's. The study found that decline in long-term memory retention began with the buildup of beta amyloid in neurons of the hippocampus, amygdala and cerebral cortex regions of the mice's brains, although the plaques and tangles characteristic of Alzheimer’s had not yet developed. When the beta amyloid was cleared away, the memory impairments disappeared; the reemergence of beta amyloid inside the neurons marked again the onset of memory problems.

Billings, L.M., Oddo, S., Green, K.N., McGaugh, J.L. & LaFerla, F.M. 2005. Intraneuronal Aβ Causes the Onset of Early Alzheimer’s Disease-Related Cognitive Deficits in Transgenic Mice. Neuron, 45(5), 675-688.

Progress toward a more targeted treatment of Alzheimer's disease

A major role in the process by which plaques develop is played by γ-secretase, an enzyme that cuts proteins in a particular place. Sometimes the γ-secretase cleavage goes wrong, causing the creation of a by-product that sticks together and precipitates (plaques). Although γ-secretase is divided into several entities, it’s been assumed that the complex acts as a homogeneous unit. However, new research has found that γ-secretase's various sub-units exhibit very diverse, tissue-specific activity. The findings should make it possible to develop medicines that are targeted on a single sub-unit and thereby have a much more specific action, with fewer unwanted side-effects.

Serneels, L. et al. 2005. Differential contribution of the three Aph1 genes to g-secretase activity in vivo. Proceedings of the National Academy of Sciences, 102, 1719-1724; published online before print January 21 2005

Certain antibodies might clear amyloid-beta proteins from brain

New research in mice may explain why certain antibodies could slow or reverse changes in the brain that are characteristic of Alzheimer’s disease. The study used an antibody that targets a particular region on the amyloid-beta protein. Animals injected with the antibody over a period of months developed fewer amyloid plaques in the brain than did control animals. It appears that the antibody draws amyloid-beta out of the brain and into the blood as a clearance mechanism. "Our work is distinguished from previous research in that we have discovered that this particular antibody can be administered into the bloodstream and need not necessarily gain access to the brain and directly attack amyloid plaque to be effective in reducing plaques. Thus, our work suggests a new mechanism by which certain anti-amyloid antibodies could be useful in preventing or treating Alzheimer’s." The research team now is working to understand the detailed mechanism of how the antibody exerts its effect. The research has potential implications for both diagnosis and treatment of Alzheimer’s disease.

DeMattos RB, Bales KR, Cummins DJ, Dodart J-C, Paul SM, Holtzman DM. Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer’s disease, Proceedings of the National Academy of Sciences Early Edition, 2(27), July 3, 2001.

Amyloid plaques follow oxidative damage to brain cells

Research into the causes of Alzheimer's Disease shows that amyloid plaques develop while the illness is taking over the brain but still not clinically evident. Accordingly, the most common scientific belief holds that those plaques contribute to or cause the oxidative damage and inflammation that occur and, ultimately, destroy brain cells. Now, a mouse-model study at the University of Pennsylvania School of Medicine has demonstrated that oxidative damage precedes the plaques. This finding is likely to have significant implications for treatment. "We know Vitamin E, which is an anti-oxidant, can temporarily slow the progression of AD for some patients. What we don't yet know is what will happen if we suppress, reduce or delay oxidative stress over the long run."

Praticò, D., Uryu, K., Leight, S., Trojanoswki, J. Q., & Lee, V. M.-Y. (2001). Increased Lipid Peroxidation Precedes Amyloid Plaque Formation in an Animal Model of Alzheimer Amyloidosis. The Journal of Neuroscience, 21(12), 4183–4187. Retrieved from

Scientists begin to unravel cause of blocked memory in Alzheimer's

Researchers at the National Institute of Environmental Health Sciences have found that a protein found in patients with Alzheimer's disease can disrupt brain signals and therefore may contribute to the memory losses of Alzheimer's disease. It appears the characteristic plaques found in the brains of Alzheimer's patients may not be the result of the disease but a cause. It is thought that the major protein of these plaques, beta-amyloid peptide, binds to a receptor in the brain, thus blocking the signals thought to be involved in learning and memory.

Pettit, D. L., Shao, Z., & Yakel, J. L. (2001). β-Amyloid1–42 Peptide Directly Modulates Nicotinic Receptors in the Rat Hippocampal Slice. The Journal of Neuroscience, 21(1), RC120–RC120. Retrieved from

Increased production of protein alpha1-antichymotrypsin found to strongly increase plaque deposits

The protein alpha1-antichymotrypsin can double the accumulation of amyloid plaque in the brains of mice, suggesting a possible new target for therapy in humans. Alpha1-antichymotrypsin (ACT) is a serin protease inhibitor, or serpin, that normally prevents enzymes known as proteases from digesting proteins. Scientists have known for some time that production of ACT is increased in the brains of patients with Alzheimer's disease, but its role has not been understood. The current study, conducted in genetically engineered mice, reveals that increased production of ACT in the brain strongly increases the build-up of amyloid proteins. It is not yet clear exactly how it does this.

Mucke, L., Yu, G.-Q., McConlogue, L., Rockenstein, E. M., Abraham, C. R., & Masliah, E. (2000). Astroglial Expression of Human α1-Antichymotrypsin Enhances Alzheimer-like Pathology in Amyloid Protein Precursor Transgenic Mice. The American Journal of Pathology, 157(6), 2003–2010. doi:10.1016/S0002-9440(10)64839-0

Enzyme found essential for nerve cells to form amyloid plaques

Scientists at Johns Hopkins have demonstrated that a specific enzyme, beta-secretase, is essential for nerve cells to form amyloid plaques, whose over-abundance is characteristic of Alzheimer's. It is one of two enzymes implicated in plaque formation. The other is gamma-secretase. "We're really encouraged by possible therapeutic implications because scientists are already designing small molecules capable of crossing the brain's blood-brain barrier." The molecules could, in theory, be fine-tuned to inhibit such enzymes as beta-secretase.

The research was presented at the annual meeting of the Society for Neuroscience in New Orleans.

Accumulation of plaque may occur because of a decrease in the molecule involved in removing it

While the excess of amyloid plaque deposits have long been recognized as a hallmark of Alzheimer's disease, it has not been known whether the problem occurs because of an over-production, or because of a failure to remove them. A study involving mice found that blood vessels are responsible for removing the beta amyloid protein in healthy brain tissue. In particular, a protein known as LRP-1 (low density lipoprotein receptor-related protein), rapidly shuttles beta amyloid out of the brain and across the blood-brain barrier to the body, which breaks it down into harmless waste products. Not only did the researchers find that removal of amyloid from the brain slowed dramatically when LRP-1 was blocked, but they also showed that healthy middle-aged mice had fewer LRP-1 molecules and shuttled amyloid out of their brains at only half the rate as young mice. It is speculated that healthy young people normally can handle the load of removing amyloid, but that plaques can occur when the LRP-1 system becomes less efficient and the body faces other challenges related to aging, such as decreased circulation. It's also possible that the protein begins accumulating more quickly, overwhelming the removal system.


Biosensor reveals new information about ADDLs

A new method using nanoscale optical biosensors allows researchers to detect and estimate the size and structure of ADDLs in cerebrospinal fluid. It’s believed that only ADDLs of a certain size cause problems for neurons in the early stages of Alzheimer’s disease. It is hoped that eventually this technology will help us diagnose Alzheimer’s accurately in living people, and aid our understanding of how ADDLs are involved in Alzheimer’s.

Haes, A.J., van Duyne, R.P., Klein, W.L. & Chang, L. 2005. The paper, ANYL 396, was presented at 9:00 a.m., Wednesday, Aug. 31, during the "New Frontiers in Ultrasensitive Analysis: Nanobiotech, Single Molecule Detection, and Single Cell Analysis" symposium.

Findings show how toxic proteins rob Alzheimer's patients of memory

Researchers have discovered a molecular mechanism that could explain why the brain damage in early Alzheimer's disease results in memory loss and not other symptoms such as loss of balance or tremors. Toxic proteins called "amyloid ß-derived diffusible ligands" (ADDLs) — first discovered last year — have been found to specifically attack and disrupt synapses, rather than the neurons themselves. By so doing they damage the neuron’s ability to communicate with other neurons. Moreover, the ADDLs target specific synapses — those where there is a gene linked to memory that is normally expressed. The attack disrupts the normal expression of the gene. The finding brings hope that the damage is reversible. ADDls are a form of amyloid beta, but differ from the better-known amyloid fibrils known as plaques, that are a hallmark of Alzheimer’s.

Lacor, P.N., Buniel, M.C., Chang, L., Fernandez, S.J., Gong, Y., Viola, K.L., Lambert, M.P., Velasco, P.T., Bigio, E.H., Finch, C.E., Krafft, G.A. & Klein, W.L. 2004. Synaptic Targeting by Alzheimer's-Related Amyloid {beta} Oligomers. Journal of Neuroscience, 24, 10191-10200.

New toxic protein found

New research has found up to 70 times more small, soluble aggregated proteins called "amyloid b-derived diffusible ligands" (ADDLs) in the brain tissue of individuals with Alzheimer's disease compared to that of normal individuals. This supports a recent theory in which ADDLs accumulate at the beginning of Alzheimer's disease and block memory function by a process predicted to be reversible. ADDLs have the ability to attack the memory-building activity of synapses, points of communication where neurons exchange information, without killing neurons. While both are a form of amyloid beta, ADDLs differ significantly from the amyloid fibrils (plaques) that are diagnostic of Alzheimer's. ADDLs are much, much smaller than fibrils. Unlike fibrils, ADDLs are soluble and diffuse between brain cells until they find vulnerable synapses. The discovery of ADDLs may help explain the poor correlation between plaques and neurological deficits.

Gong, Y. et al. 2003. Alzheimer's disease-affected brain: Presence of oligomeric A β ligands (ADDLs) suggests a molecular basis for reversible memory loss. PNAS, 100, 10417-10422.

Amyloid beta production

Amyloid beta can disrupt neural communication without clumping

Two separate studies have found that minute clumps of amyloid beta (not accumulated into plaque) severely disrupt neurotransmission and inhibit delivery of key proteins in Alzheimer's. One study found that the particles activate an enzyme, CK2, which in turn disrupts the "fast axonal transport" system inside the neuron, while the other found that activation of CK2 blocks neurotransmission at the synapse. It’s suggested that disruptions in the fast axonal transport system are probably key elements in the pathogenesis of Alzheimer's and other adult-onset neurodegenerative diseases, such as Parkinson's and ALS. A prior study also found that activation of another enzyme, GSK3, also disrupts the fast axonal transport system. The new findings suggest the possibility of designing a drug to protect the fast axonal transport system.

Pigino, G. et al. 2009. Disruption of fast axonal transport is a pathogenic mechanism for intraneuronal amyloid beta. PNAS, 106 (14), 5907-5912.

Moreno, H. et al. 2009. Synaptic transmission block by presynaptic injection of oligomeric amyloid beta. PNAS, 106 (14), 5901-5906. Full text at

Why stroke and hypertension may increase risk of Alzheimer's

New findings of the presence of beta amyloid in the brain of a mouse that overproduces a protein called p25 may help explain the occurrence of sporadic Alzheimer's (the more common form of the disease) and also why stroke and high blood pressure increase the likelihood of developing Alzheimer's. Researchers are now testing potential compounds to halt, or even prevent, the complex cascade of events caused by the presence of p25 that lead to neurodegeneration. The work may also suggest an intervention after stroke to lower or prevent additional risk of Alzheimer's.

The report was presented on June 15 at the annual meeting of the American Society for Biochemistry and Molecular Biology (ASBMB)/8th International Union of Biochemistry and Molecular Biology Conference (IUBMB) in Boston.

Gene targeting prevents memory loss in Alzheimer's disease model

A new mouse study presents new evidence that beta-amyloid is directly responsible for causing the memory loss seen in Alzheimer's, and provides compelling evidence for the therapeutic potential of inhibiting an enzyme, beta-secretase (BACE1), required for the production of beta-amyloid. The mice were genetically engineered to lack the enzyme.

Ohno, M., Sametsky, E.A., Younkin, L.H., Oakley, H., Younkin, S.G., Citron, M., Vassar, R. & Disterhoft, J.F. 2004. BACE1 Deficiency Rescues Memory Deficits and Cholinergic Dysfunction in a Mouse Model of Alzheimer's Disease. Neuron, 41, 27-33.

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Older news items (pre-2010) brought over from the old website

Immunization with AB42 does not prevent dementia despite clearing associated brain plaques

Disappointingly, analysis of 80 Alzheimer's patients who had been involved in trialing immunisation against amyloid-β in September 2000, has found that, despite a lower level of amyloid-β plaques, there was no improved survival or increased time to severe dementia in those who were immunised.

Holmes, C. et al. 2008. Long-term effects of AB42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial. The Lancet, 372 (9634), 216-223.

Vaccine prevents Alzheimer's

A vaccine has successfully prevented the development of amyloid plaques and tau tangles in the brains of genetically engineered mice. The vaccinated mice also demonstrated normal learning skills and functioning memory. There were no major side-effects. Human trials are still a few years off.

Frazer, M.E. et al. 2008. Reduced Pathology and Improved Behavioral Performance in Alzheimer's Disease Mice Vaccinated With HSV Amplicons Expressing Amyloid-β and Interleukin-4. Molecular Therapy, 16, 845-853.

Alzheimer's vaccine clears plaque but doesn't improve memory

A two-year canine study has revealed that although a promising vaccine being tested for Alzheimer's disease clears beta-amyloid plaques from the brain, it doesn’t seem to help restore lost learning and memory abilities. Autopsies showed that although plaques had been cleared from multiple brain regions, damaged neurons remained. The findings suggest that simply treating beta-amyloid plaques may have only limited clinical benefit if started after there is significant plaque growth, and a combination of vaccination with other therapies aimed at repairing damaged neurons may be best.

Head, E. et al. 2008. A Two-Year Study with Fibrillar β-Amyloid (Aβ) Immunization in Aged Canines: Effects on Cognitive Function and Brain Aβ. Journal of Neuroscience, 28, 3555-3566.

Transdermal vaccine effective in treating Alzheimer's disease in mice

Previous research on an Alzheimer's vaccine proven safe and effective in an animal model was suspended when the initial clinical trial caused brain inflammation and death in a small percentage of patients. A new mouse study has now had success with a transdermal method of delivery (a skin patch), that doesn’t appear to trigger the toxic reaction of past immunization strategies. Further research is needed to assess whether the transdermal vaccine can curb memory loss as well as reduce Ab plaque.

Nikolic, W.V. et al. 2007. Transcutaneous -amyloid deposits without T cell infiltration and microhemorrhage. Proceedings of the National Academy of Sciences, 104 (7), 2507-2512.

Hopeful results from interrupted Alzheimer's vaccine study

Phase 2 of a human clinical trial vaccinating patients with beta-amyloid was halted in 2002 when some participants developed brain inflammation. Participants continued to be monitored, however, and results show that participants whose immune systems mounted a response against beta amyloid performed significantly better on a series of memory tests than those who received a placebo injection (but not on 5 tests often used to diagnose dementia). There were also signs of reduced levels of tau protein (a protein considered a sign of cell death) in those who had an immune response. As a result, new trials are underway, this time using humanized antibodies rather than beta amyloid itself. The antibodies should help trigger the immune system to attack beta amyloid, but will be cleared by the body soon after injection.

Gilman, S., Koller, M., Black, R.S., Jenkins, L., Griffith, S.G., Fox, N.C., Eisner, L., Kirby, L., Boada Rovira, M., Forette, F. & Orgogozo, J-M. for the AN1792(QS-21)-201 Study Team. 2005. Clinical effects of Aß immunization (AN1792) in patients with AD in an interrupted trial. Neurology, 64, 1553-1562.

Fox, N.C., Black, R.S., Gilman, S., Rossor, M.N., Griffith, S.G., Jenkins, L. & Koller, M. for the AN1792(QS-21)-201 Study Team. Effects of Aß immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease. Neurology, 64, 1563-1572.

Progress on Alzheimer's vaccine

Efforts to create a vaccine for Alzheimer’s have been hindered by potential side effects — some human participants in an earlier trial developed severe inflammation in the brain. A mouse study has now substantially increased the safety of the vaccine by including a tetanus toxin to alter the immune response. Future studies are planned using the herpes virus.

Bowers, W.J., Mastrangelo, M.A., Stanley, H.A., Casey, A.E., Milo, L.J.Jr. & Federoff, H.J. 2004. HSV amplicon-mediated Ab vaccination in Tg2576 mice: differential antigen-specific immune responses. Neurobiology of Aging, available online 25 June 2004.

Mice immunized against Alzheimer's

Using a new vaccine, NYU School of Medicine researchers have prevented the development of Alzheimer's disease in mice genetically engineered with the human gene for the disease. The researchers are optimistic that this new vaccine is safer than one already being tested in early human clinical trials. The new vaccine, modeled on a fragment of a protein called amyloid, which is most frequently implicated in causing Alzheimer's, reduced the amount of amyloid plaque in the brains of mice by 89 percent. At the same time, the vaccine reduced the amount of soluble amyloid beta in the brain by 57 percent. Early clinical trials of the new vaccine could begin within one year.

Sigurdsson, E. M., Scholtzova, H., Mehta, P. D., Frangione, B., & Wisniewski, T. (2001). Immunization with a Nontoxic/Nonfibrillar Amyloid-β Homologous Peptide Reduces Alzheimer’s Disease-Associated Pathology in Transgenic Mice. The American Journal of Pathology, 159(2), 439–447. doi:10.1016/S0002-9440(10)61715-4

A vaccine for Alzheimer's

A vaccine may help prevent and treat the disabling memory loss and cognitive impairment of Alzheimer's disease. Alzheimer's occurs when amyloid-beta peptides accumulate in the brain, forming plaque. While previous studies have shown that vaccinating mutated mice with this amyloid-beta peptide could remove the plaque deposits, there was never any evidence of improvement in brain function, until now. The researchers also believe this study provides the final element of proof that Alzheimer's is initiated by amyloid-beta peptides. The researchers believe clinical trials could begin on human subjects within the year.

Johnson, J. D., McDuff, S. G. R., Rugg, M. D., & Norman, K. A. (2009). Recollection, Familiarity, and Cortical Reinstatement: A Multivoxel Pattern Analysis. Neuron, 63(5), 697–708. doi:10.1016/j.neuron.2009.08.011

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Pilot drug studies

Older news items (pre-2010) brought over from the old website

Tarenflurbil fails clinical trial

In another example of a drug that worked in mice but failed to show a benefit for patients, a study has found that the drug tarenflurbil, which supposedly suppresses the accumulation of amyloid plaque—did not slow cognitive decline or loss of usual daily activities (and was moreover associated with adverse effects including anemia, pneumonia, and herpes zoster). Although the drug showed promise in a small clinical trial, the results were negative in this larger, randomized trial, involving 1684 patients with mild Alzheimer’s. It’s suggested that rather than focusing on Alzheimer's disease and its specific characteristics, we should see dementia as a confluence of three common disease processes—Alzheimer's disease, vascular brain injury, and Lewy body disease.

Jonsson, M., Edman, Å., Lind, K., Rolstad, S., Sjögren, M., & Wallin, A. (2009). Apathy is a prominent neuropsychiatric feature of radiological white-matter changes in patients with dementia. International Journal of Geriatric Psychiatry, 9999(9999), n/a. doi: 10.1002/gps.2379.

Neurogenesis improved in Alzheimer mice

Studies of adult neurogenesis in genetically engineered mice have revealed two main reasons why amyloid-beta peptides and apolipoprotein E4 impair neurogenesis, and identified drug treatments that can fix it. The findings point to a deficit in GABAergic neurotransmission or an imbalance between GABAergic and glutamatergic neurotransmission as an important contributor to impaired neurogenesis in Alzheimer’s. While stem cell therapy for Alzheimer’s is still a long way off, these findings are a big step toward that goal.

Gang Li et al. 2009. GABAergic Interneuron Dysfunction Impairs Hippocampal Neurogenesis in Adult Apolipoprotein E4 Knockin Mice. Cell Stem Cell, 5 (6), 634-645.

Binggui Sun et al. 2009. Imbalance between GABAergic and Glutamatergic Transmission Impairs Adult Neurogenesis in an Animal Model of Alzheimer's Disease. Cell Stem Cell, 5 (6), 624-633.

Protein identified that counterbalances Alzheimer's proteins

A mouse study has revealed that a protein called Reelin may provide a new approach to tackling Alzheimer’s. Reelin activates and strengthens the response of the NMDA receptor, which plays an important role in coordinating chemical signals between adjacent nerve cells. In the presence of too much amyloid-beta protein (as occurs in an Alzheimer’s brain), the receptor migrates into the cell, reducing the cell's sensitivity to incoming signals. However, with strong concentrations of Reelin, the receptor remains active and the cell continues receiving normally. The findings also make a connection with ApoE4 — the receptor that binds to ApoE also binds to Reelin, and is part of the complex that controls the sensitivity of the NMDA receptors.

Durakoglugil, M. S., Chen, Y., White, C. L., Kavalali, E. T., & Herz, J. (2009). Reelin signaling antagonizes β-amyloid at the synapse. Proceedings of the National Academy of Sciences, 106(37), 15938-15943. doi: 10.1073/pnas.0908176106.

Epilepsy drug may help Alzheimer's patients

A study involving genetically engineered mice has found that mice given the anti-seizure drug valproic acid soon after onset of the disease showed improved memory and reduced plaques. The acid worked by blocking the cascade of reactions that leads to beta-amyloid plaques. Valproic acid helped mice less as their disease progressed.

Qing, H. et al. 2008. Valproic acid inhibits Aβ production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models. The Journal of Experimental Medicine, Published online October 27.

New drug for Alzheimer’s

A pilot study of 321 people with mild and moderate Alzheimer's disease has found that those who took the new drug Rember for 50 weeks demonstrated a dramatically smaller reduction (81%) in mental decline compared with those on the placebo. Those on rember did not experience a significant decline in their mental function over 19 months, while those on a placebo got worse. Rember is the first drug to act on the tau protein. A "phase 3" trial is planned for next year, involving a larger group of people with the disease, and if that is successful, the drug could be available by 2012.

The findings were presented at the international conference on Alzheimer's disease in Chicago.

Early study reveals new drug could improve executive function in Alzheimer's patients

A trial of a new drug called PBT2 has been found to improve two indicators of executive function in patients with Alzheimer's disease, and reduces levels of amyloid β in the cerebrospinal fluid. There was no significant effect on memory, but this could be because memory functions deteriorate more slowly than executive ones during the early stage, making changes harder to detect in such a short study. The parent compound to PBT2 is clioquinol.

Lannfelt, L. et al. 2008. Safety, efficacy, and biomarker findings of PBT2 in targeting Aβ as a modifying therapy for Alzheimer's disease: a phase IIa, double-blind, randomised, placebo-controlled trial. The Lancet Neurology, 7 (9), 779-786.

Dimebon significantly improves Alzheimer's symptoms

A study involving 183 Russian patients with mild-to-moderate Alzheimer’s has found that a drug previously used as an antihistamine (dimebon) significantly improved cognitive performance. Moreover, it demonstrated increasing benefits over 12 months, which no currently approved therapies do.

Doody, R.S. et al. 2008. Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer's disease: a randomised, double-blind, placebo-controlled study. The Lancet, 372 (9634), 207-215.

Tarenflurbil slows decline of mild Alzheimer's patients

A trial of 210 patients with mild to moderate Alzheimer’s has found that those with mild Alzheimer’s who received 800mg of tarenflurbil twice a day for a year experienced a rate of decline 46% lower than placebo patients in the activities of daily living scale, and a 36% reduction in the pace of decline in global function.  In those with moderate Alzheimer’s, neither 400mg or 800mg of tarenflurbil had a significant effect, and indeed impacted negatively on a third measure of global function. Patients with mild Alzheimer’s who took 800mg for 24 months had lower rates of decline for all three primary outcomes than those who took it for a shorter period.

Wilcock, G.K. et al. 2008. Efficacy and safety of tarenflurbil in mild to moderate Alzheimer's disease: a randomised phase II trial. Lancet Neurology, 7, 483-493.

Potential new drug target identified

A mouse study has successfully reduced the production of beta-amyloid peptides, and improved memory. These peptides are produced when enzymes cut APP at two places, called the beta-secretase and gamma-secretase sites. Previous research has focused on a mutant beta-secretase sequence only seen in one extended family of patients, the so-called Swedish mutation. The new study identifies a different enzyme, called Cathepsin B (CatB), which works to cut the normal beta-secretase site in more than 99% of patients with Alzheimer’s. Two compounds that inhibit CatB were successfully tested, producing great improvement in memory, as well as reduced brain levels of beta amyloid.

Hook, V.Y.H., Kindy, M. & Hook, G. 2008. Inhibitors of Cathepsin B Improve Memory and Reduce β-Amyloid in Transgenic Alzheimer Disease Mice Expressing the Wild-type, but Not the Swedish Mutant, β-Secretase Site of the Amyloid Precursor Protein. Journal of Biological Chemistry, 283, 7745-7753.

PLMI factor in sleep disturbance for dementia patients

A study of 102 people diagnosed with both cognitive impairment and sleep disturbance (average nightly sleep of seven or less hours and daytime sleep of 30 minutes or longer) found that periodic leg movement disorder (a condition that causes people to jerk and kick their legs every 20 to 40 seconds during sleep) was predictive of reduced total sleep time in older adults with Alzheimer disease and related dementias. Given that sleep disturbance in persons with dementia is a highly prevalent and disabling symptom, and sedative-hypnotics are not recommended, this finding is important because it suggests treatment of periodic leg movements may be beneficial.

Richards, K.C. et al. 2008. Periodic Leg Movements Predict Total Sleep Time in Persons with Cognitive Impairment and Sleep Disturbance. SLEEP, 31(2), 224-230.

Reduction of tau protein protects against Alzheimer’s

A study using genetically engineered mice has found that when tau protein was reduced their memory function was retained and they lived a normal lifespan, even though amyloid-beta levels weren’t affected. They were also made mice more resistant to epileptic seizures.

Roberson, E.D. et al. 2007. Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model. Science, 316 (5825), 750-754.

Marijuana may slow progression of Alzheimer's disease

New evidence suggests that marijuana — which has strong anti-inflammatory effects — may contain compounds that slow the memory loss associated with Alzheimer's disease. Treatment with a synthetic compound similar to marijuana (WIN-55212-2) reduced inflammation in older rats and substantially improved their memories.

The researchers presented their findings October 18 at the annual Society for Neuroscience meeting in Atlanta.

New drug reduces plaque and tangles in Alzheimer's mice

Alzheimer's mice that received a compound known as AF267B for eight weeks performed significantly better on a spatial memory test than untreated mice did. A different memory test that involved associating a place with a shock was not affected. The drug was found to reduce plaques and tangles in the hippocampus but not in the amygdala. AF267B seems to work in part by enhancing the activity of receptors for the neurotransmitter acetylcholine, and boosting the levels of an enzyme called alpha secretase, which blocks the production of beta-amyloid proteins. Suppressing the M1 receptors worsened the condition and performance of Alzheimer’s mice, confirming the important role of M1 receptors in modulating the plaques and tangles characteristic of Alzheimer’s.

Caccamo, A. et al. 2006. M1 Receptors Play a Central Role in Modulating AD-like Pathology in Transgenic Mice. Neuron, 49, 671-682.

New compound stops brain cell degeneration in Alzheimer's disease

A new orally administered compound specifically targeted to suppress brain cell inflammation and neuron loss associated with Alzheimer's disease has been developed. The compound, MW01-5-188WH, is rapidly absorbed by the brain and is non-toxic. It selectively inhibits production of pro-inflammatory proteins called cytokines by glia, giving it relevance for several neurodegenerative disorders. The compound suppressed brain inflammation and neuron dysfunction in the hippocampus and protected against cognitive decline in genetically engineered mice. The compound also restored normal levels of markers of synaptic dysfunction in the hippocampus and attenuated Alzheimer's-like behavioral deficits. The compound represents a new approach to Alzheimer’s therapy.

Ranaivo, H.R., Craft, J.M., Hu, W., Guo, L., Wing, L.K., Van Eldik, L.J. & Watterson, D.M. 2006. Glia as a Therapeutic Target: Selective Suppression of Human Amyloid-Induced Upregulation of Brain Proinflammatory Cytokine Production Attenuates Neurodegeneration. Journal of Neuroscience, 26, 662-670.

Testosterone improves quality of life

A 24-week study involving 16 male patients diagnosed with mild Alzheimer disease and 22 healthy male controls found that Alzheimer’s patients who received daily testosterone treatment showed significant improvement on a quality-of-life instrument that encompasses memory, interpersonal relationships, physical health, energy, living situation and overall well-being, however improvement in memory or other cognitive skills using cognitive tests did not reach significance. Among healthy controls, those receiving testosterone showed a non-significant trend toward greater improvement in self-rated quality of life.

Lu, P.H. et al. 2006. Effects of Testosterone on Cognition and Mood in Male Patients With Mild Alzheimer Disease and Healthy Elderly Men. Archives of Neurology, 63.
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Natural compound from 'pond scum' shows potential activity against Alzheimer's

A compound isolated from a cyanobacterium, a type of blue-green algae (‘pond scum’) shows promise of becoming a natural drug candidate for fighting Alzheimer's. Nostocarboline (the newly isolated compound) is a potent inhibitor of cholinesterase, with a potency comparable to galanthamine.

Becher, P.G., Beuchat, J., Gademann, K. & Jüttner, F. 2005. Nostocarboline: Isolation and Synthesis of a New Cholinesterase Inhibitor from Nostoc 78-12A. Journal of Natural Product, 68(12), 1793–1795.

Gas-blockers might slow down Alzheimer's disease

Beta-amyloid is known to cause brain cells to make an inhibitor of an enzyme that triggers the production of nitric oxide (iNOS). This enzyme is normally turned on during infection and is needed to help immune cells destroy invading pathogens, but it is not normally found in the brain, where it may cause cellular damage that destroys neurons. Although it’s long been known that iNOS is present in the brain lesions of Alzheimer’s patients, it hasn’t been known whether its presence makes things worse. A new study has now shown that Alzheimer's-prone mice that lack iNOS live twice as long and develop fewer brain lesions than iNOS-expressing mice. The researchers suggest that iNOS inhibitors might turn out to be an effective in slowing the progression of Alzheimer's disease.

Nathan, C. et al. 2005. Protection from Alzheimer's-like disease in the mouse by genetic ablation of inducible nitric oxide synthase. Journal of Experimental Medicine, 202, 1163-1169.

New memory drug works best in combination with older drug

An experimental drug – a compound known as SGS742 – has been successful in animal studies in improving memory, and is now in human clinical trials. The drug works by blocking certain chemicals that interfere with memory formation, thus enabling better acquisition and retention of new information. It alters the activity of gene control machinery that is important for memory consolidation. It was most effective when used in conjunction with Aricept, an established Alzheimer’s drug.

Helm, K.A., Haberman, R.P., Dean, S.L., Hoyt, E.C., Melcher, T., Lund, P.K. & Gallagher, M. 2005. GABAB receptor antagonist SGS742 improves spatial memory and reduces protein binding to the cAMP response element (CRE) in the hippocampus. Neuropharmacology, 48(7), 956-64.

Chemical decoy shows promise for slowing Alzheimer's

A chemical polymer shows promise in cell culture studies of slowing Alzheimer’s by blocking the toxic brain proteins thought to cause the disease. The likely candidate for any drugs developed from this approach would be people at increased risk of Alzheimer’s, who haven’t yet developed signs of the disease.

Good, T. & Patel, D. 2005. BIOT 421 Development of biomimetic materials for Alzheimer's disease. Presented at 2:05 p.m., Thursday, March 17, at the Convention Center, Room 31A, during the "Tissue Engineering/Biomaterials" symposium at the 229th national meeting of the American Chemical Society.

Antibody treatment partially reverses nerve damage in Alzheimer disease

A mouse study has had success in significantly decreasing structural nerve damage in the brains of mice with Alzheimer’s, by administering an beta amyloid antibody treatment to the brain surface.

Brendza, R.P. et al. 2005. Anti-Aß antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice.Journal of Clinical Investigation, 115, 428-433.

Rolipram - a potential new treatment

In a mouse study, a phosphodiesterase 4 inhibitor, rolipram, was found to improve memory in both long-term potential and contextual learning. Rolipram's protective effect is due to its ability to modify gene expression, making brain synapses more resistant to the insult caused by the accumulation of Ab. The beneficial effect of rolipram treatment was found to extend for at least 2 months after the end of one course of the treatment, and was more effective in the later stages of the disease.

Gong, B., Vitolo, O.V., Trinchese, F., Liu, S., Shelanski, M. & Arancio, O. 2004. Persistent improvement in synaptic and cognitive functions in an Alzheimer mouse model after rolipram treatment. Journal of Clinical Investigation, 114, 1624-1634.

Keeping blood pressure & cholesterol low may help some dementia patients more than Alzheimer's drugs

A comprehensive review of all recent medical studies on mixed dementia, vascular dementia and Alzheimer's suggests that efforts to treat cardiovascular risk factors, especially high blood pressure, may be more effective for many than memory drugs in protecting brain function.

Langa, K.M., Foster, N.L. & Larson, E.B. 2004. Mixed Dementia: Emerging Concepts and Therapeutic Implications. JAMA, 292, 2901-2908.

New type of Alzheimer's drug on trial

A clinical trial is commencing to test the effectiveness of a new type of drug, called Alzhemed, that attacks amyloid. The trial will last 18 months and will enroll about 950 Alzheimer's patients with a mild-to-moderate form of the disease, from centers around the United States and Canada. The drug actually physically combines with amyloid to prevent plaque formation, and is also expected to inhibit the inflammatory response associated with amyloid buildup in Alzheimer's.

Blood pressure drugs may slow deterioration of Alzheimer's

A study involving 162 people in Japan living in long-term care facilities with mild to moderate Alzheimer's disease and high blood pressure has found that certain blood pressure drugs may slow the deterioration of Alzheimer's disease. The results, while interesting, will need to be replicated in carefully controlled, randomized, blinded studies.

Ohrui, T., Tomita, N., Sato-Nakagawa, T., Matsui, T., Maruyama, M., Niwa, K., Arai, H. & Sasaki, H. 2004. Effects of brain-penetrating ACE inhibitors on Alzheimer disease progression. Neurology, 63, 1324-1325.

Anti-cholesterol drug treats Alzheimer's disease in mice

A drug that jams a key enzyme regulating cholesterol (CP-113,818) has been found to drastically reduce the levels of amyloid plaque in genetically engineered mice. The drug has not been tested in clinical trials, but another ACAT inhibitor, avasimibe, is now in final clinical trials as a treatment for vascular disease and atherosclerosis.

Hutter-Paier, B., Huttunen, H.J., Puglielli, L., Eckman, C.B., Kim, D.Y., Hofmeister, A., Moir, R.D., Domnitz, S.B., Frosch, M.P., Windisch, M. & Kovacs, D.M. 2004. The ACAT Inhibitor CP-113,818 Markedly Reduces Amyloid Pathology in a Mouse Model of Alzheimer's Disease. Neuron, 44 (2), 227–238.

Protein found that dissolves amyloid fibers

Amyloid plaque is extremely tough — so tough researchers have been unable to find a means to attack them. A new study suggests that yeast may be the means. Oddly, the yeast protein seems to be involved both in making amyloid fibers, and in dissolving them. The yeast protein Sup35 sometimes forms amyloid fibers in yeast cells — this is part of the cell's normal biology, changing the types of proteins that the cell makes. Another protein — Hsp104 — appears to affect Sup35's ability to form amyloid fibers. When a yeast cell contained either high amounts of Hsp104 or none at all, amyloid fibers never formed. But when Hsp104 levels were small, the fibers flourished. In the latest study, researchers found that small amounts of Hsp104 catalyzed the formation of amyloid fibers, but large levels of the protein actually caused the fibers to dissolve. Interestingly, Hsp104 belongs to a class of proteins that sometimes are influenced by environmental factors.

Shorter, J., & Lindquist, S. (2004). Hsp104 Catalyzes Formation and Elimination of Self-Replicating Sup35 Prion Conformers. Science, 304(5678), 1793–1797. doi:10.1126/science.1098007

Clioquinol slowed progression of cognitive decline in Alzheimer's patients

A new clinical trial has found that the drug Clioquinol slowed the progression of cognitive decline in a group of 36 patients with moderate to severe Alzheimer’s, over a period of 24 weeks. PBT-1 (Clioquinol) is a chemical that binds zinc and copper, and has been shown to lower the levels of beta-amyloid and the associated toxicity in the brains of transgenic mice used as a model of Alzheimer's disease.

Ritchie, C.W. et al. 2003. Metal-Protein Attenuation With Iodochlorhydroxyquin (Clioquinol) Targeting A β Amyloid Deposition and Toxicity in Alzheimer Disease: A Pilot Phase 2 Clinical Trial. Archives of Neurology, 60, 1685-1691.

Cancer drug may help against Alzheimer's too

The drug Gleevec, approved for treatment of chronic myelogenous leukemia (CML) over two years ago, has been found to reduce the level of beta-amyloid in immature rat neurons and cultured human cells. The drug also significantly reduced the levels of amyloid peptides in live guinea pigs (who have amyloid peptides comparable to those found in humans). While still preliminary, the work may indicate a new approach to treating Alzheimer’s.

Netzer, W.J. et al. 2003. Gleevec inhibits β-amyloid production but not Notch cleavage. PNAS, 100, 12444-12449.

New Drug for Moderate-to-Severe Alzheimer's

Four drugs — donepezil, galantamine, rivastigmine, and tacrine — are approved for treatment of mild-to-moderate Alzheimer's disease in the U.S., but there are no approved treatments for severe AD. Now an industry-sponsored study has examined memantine for this use. The study involved 252 patients with moderate-to-severe AD, over a period of 28 weeks. Patients were evaluated on 7 tests of cognition, functional capacity, and behavior. Outcomes were significantly better with memantine than with placebo on 4 of these scales, and no significant adverse events were noted. It is not clear yet how clinically meaningful these small improvements are. Memantine has been approved for use in Europe.

Reisberg, B., Doody, R., Stöffler, A., Schmitt, F., Ferris, S. & Möbius, H.J. 2003. Memantine in moderate-to-severe Alzheimer's disease. New England Journal of Medicine, 348, 1333-41.

DHEA supplement shows no effect on Alzheimer's

The supplement dehydroepiandrosterone, or DHEA, had no effect on Alzheimer's patients who took the supplement for six months. A transient benefit on cognitive performance occurred at three months, but was not statistically significant. Of the 58 people who started the study, 46 completed three months of treatment and 33 completed six months of treatment. The small size of the study and the high number of people who dropped out may limit the findings of the study.

Wolkowitz, O.M., Kramer, J.H., Reus, V.I., Costa, M.M., Yaffe, K., Walton, P., Raskind, M., Peskind, E., Newhouse, P., Sack, D., De Souza, E., Sadowsky, C., Roberts, E. & the DHEA-Alzheimer’s Disease Collaborative Research Group. 2003. DHEA treatment of Alzheimer’s disease: A randomized, double-blind, placebo-controlled study. Neurology, 60, 1071-1076.

Designer chemical offers Alzheimer's hope

Researchers at the University of Illinois at Chicago have designed and synthesized highly potent inhibitor compounds that could lead to an effective treatment for Alzheimer’s disease. In earlier work, the researchers had designed an inhibitor that blocks the action of one of two enzymes thought to be responsible for Alzheimer’s disease. This enzyme, called memapsin 2, is responsible for producing beta-amyloid, which forms the plaques so characteristic of Alzheimer’s disease. The inhibitor was reported in the Journal of the American Chemical Society last year and was shown to be effective in test tube experiments. However, while useful as a model, the inhibitor was too big to be effective in drug therapy. What is needed is a compound small enough to cross the blood-brain barrier. This latest paper reports on a new, smaller, generation of inhibitors designed and tested in the laboratory.

Golestani, N., Molko, N., Dehaene, S., LeBihan, D., & Pallier, C. (2007). Brain Structure Predicts the Learning of Foreign Speech Sounds. Cereb. Cortex, 17(3), 575–582. doi:10.1093/cercor/bhk001

Naturally occurring protein could slow Alzheimer's disease

A cholesterol-lowering protein produced by the body, Apolipoprotein A-1, might be able to slow the progression of Alzheimer's disease.
Everyone has some quantity of Apo-A, in their body. It is produced in the small intestine and the liver and is known to help prevent coronary heart disease. At normal levels, the protein clears cholesterol throughout the body, including in the brain. The scientists speculate that boosting Apo-A levels may also help clear beta amyloid, an important part of the Alzheimer's disease plaques that strangle normal brain cells. Further testing is needed to confirm the role of Apo-A in animals and its relation with Alzheimer's, before any human trials could begin.

Koldamova, R. P., Lefterov, I. M., Lefterova, M. I., & Lazo, J. S. (2001). Apolipoprotein A-I Directly Interacts with Amyloid Precursor Protein and Inhibits Aβ Aggregation and Toxicity†. Biochemistry, 40(12), 3553–3560. doi:10.1021/bi002186k

Why Vitamin E might slow the progress of Alzheimer's

A chemical called methionine (an amino acid found in beta-amyloid) may be the source of the toxic free radicals produced by the amyloid-beta peptide. Recent studies have demonstrated that higher than normal doses of vitamin E may slow the advance of Alzheimer's in some people with late stages of the disease. The current study provides a possible explanation for this link. Vitamin E, an antioxidant, appears to work by destroying free radicals (oxidants) produced by amyloid.

The study was presented at the 2000 International Chemical Congress of Pacific Basin Societies.

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Diet & supplements for Alzheimer's

Older news items (pre-2010) brought over from the old website

Caffeine reverses memory impairment in Alzheimer's mice

Consistent with earlier indications that moderate caffeine consumption may protect against memory decline, a study of genetically engineered mice has found that when the old mice began to show memory impairment, those given caffeine for 2 months performed as well as normal aged mice on cognitive tests, while those given plain drinking water continued to do poorly. The Alzheimer's mice received the equivalent of five 8-oz. cups of regular coffee a day (or two cups of Starbucks coffee, or 14 cups of tea). Moreover, the brains of the caffeinated mice showed nearly a 50% reduction in levels of beta amyloid. The effect appears to be through suppression of both β-secretase and presenilin 1 /g-secretase expression. Caffeine had this effect only on those with Alzheimer’s; normal mice given caffeine through adulthood showed no cognitive benefit.

Arendash, G.W. et al. 2009. Caffeine Reverses Cognitive Impairment and Decreases Brain Amyloid-β Levels in Aged Alzheimer's Disease Mice. Journal of Alzheimer's Disease, 17 (3), 661-680.

Cao, C. et al. 2009. Caffeine Suppresses Amyloid-β Levels in Plasma and Brain of Alzheimer's Disease Transgenic Mice. Journal of Alzheimer's Disease, 17 (3), 681-697.

Vitamin B3 reduces Alzheimer's symptoms, lesions

High doses of nicotinamide, a form of vitamin B3, has been found to dramatically lower levels of tau protein in mice with Alzheimer's disease. The vitamin also increased proteins that strengthen microtubules, the scaffolding within brain cells along which information travels. Not only did the vitamin prevent memory loss in Alzheimer’s mice, it also slightly improved cognitive performance in normal mice. Nicotinamide is a water-soluble vitamin sold in health food stores. It generally is safe but can be toxic in very high doses. Clinical trials have shown it benefits people with diabetes complications and has anti-inflammatory properties that may help people with skin conditions. Clinical trials with Alzheimer’s patients are now underway.

Green, K.N. et al. 2008. Nicotinamide Restores Cognition in Alzheimer's Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau. Journal of Neuroscience, 28, 11500-11510.

Vitamin E may help Alzheimer's patients live longer

A study of 847 Alzheimer's patients has found that those who took 1,000 international units of vitamin E twice a day, were 26% less likely to die over a five-year period than people who didn't take vitamin E.  It also appears that taking vitamin E plus a cholinesterase inhibitor may be more beneficial than taking either agent alone.

The research was presented at the American Academy of Neurology Annual Meeting in Chicago, April 12 – April 19.

Omega-3 fatty acids may slow cognitive decline in some patients with very mild Alzheimer's disease

Several studies have shown that eating fish, which is high in omega-3 fatty acids, may protect against Alzheimer's disease. A Swedish study has now tested whether supplements could have similar effects. Patients with mild-to-moderate Alzheimer’s who took 1.7 grams of DHA and .6g of EPA showed the same rate of cognitive decline as those taking a placebo, however, among a subgroup of 32 patients with very mild cognitive impairment, those who took the fatty acids experienced less decline in six months compared with those who took placebo. It may be that anti-inflammatory effects are an important reason for the benefit, potentially explaining why effects were seen only in those with very early-stage disease, when levels of inflammation seem to be higher.

Freund-Levi;, Y. et al. 2006. w-3 Fatty Acid Treatment in 174 Patients With Mild to Moderate Alzheimer Disease: OmegAD Study: A Randomized Double-blind Trial. Archives of Neurology, 63, 1402-1408.

Dietary supplements offer new hope for Alzheimer's patients

A "cocktail" of dietary supplements (omega-3 fatty acids, uridine and choline) has been found to dramatically increase the amount of membranes that form brain cell synapses in gerbils. The treatment is now in human clinical trials. It is hoped that such treatment may significantly delay Alzheimer's disease. The treatment offers a different approach from the traditional tactic of targeting amyloid plaques and tangles. Choline can be found in meats, nuts and eggs, and omega-3 fatty acids are found in a variety of sources, including fish, eggs, flaxseed and meat from grass-fed animals. Uridine, which is found in RNA and produced by the liver and kidney, is not obtained from the diet, although it is found in human breast milk.

Wurtman, R.J., Ulus, I.H., Cansev, M., Watkins, C.J., Wang L. & Marzloff, G. 2006. Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. Brain Research, Available online ahead of print 21 April 2006.

Compound in wine reduces levels of Alzheimer's disease-causing peptides

In cell studies, resveratrol has been found to lower levels of amyloid-beta peptides. Resveratrol is a natural compound occurring in abundance in grapes, berries and peanuts. The highest concentration has been reported in wines prepared from Pinot Noir grapes. The anti-amyloidogenic effect of resveratrol observed in cell cultures does not however necessarily mean that the beneficial effect can result simply from eating grapes or drinking wine. Further research aims to develop more active and more stable compounds.

Marambaud, P., Zhao, H. & Davies, P. 2005. Resveratrol Promotes Clearance of Alzheimer's Disease Amyloid- Peptides. Journal of Biological Chemistry, 280, 37377-37382.

Clinical diagnosis of Alzheimer's may be delayed with donepezil

In a study of people with mild cognitive impairment, those who took the drug donepezil were at reduced risk of progressing to a diagnosis of Alzheimer's during the first years of the trial, but by the end of the 3-year study there was no benefit from the drug. Of the 769 participants, 212 developed possible or probable Alzheimer’s within the 3-year study period; the donepezil group's risk of progression to a diagnosis of Alzheimer’s was reduced by 58% one year into the study, and 36% at 2 years, but no risk reduction at the end of three years. Vitamin E was also tested in the study and was found to have no effect at any point in the study.

Petersen, R.C. et al. 2005. Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment. New England Journal of Medicine, 352 (23), 2379-2388.

Pilot study points to healing power of turmeric

A study using genetically engineered mice has found that those mice on a diet rich in curcumin (the yellow pigment in the curry spice turmeric) developed 85% few Alzheimer’s plaques then the control group. Curcumin has antioxidant, anti-inflammatory, and cholesterol lowering properties, and has long been used in India as treatment for a variety of ailments. A human trial involving 33 Alzheimer's patients will soon commence.

Yang, F., Lim, G.P., Begum, A.N., Ubeda, O.J., Simmons, M.R., Ambegaokar, S.S., Chen, P.P., Kayed, R., Glabe, C.G., Frautschy, S.A. & Cole, G.M. 2004. Curcumin inhibits formation of Abeta oligomers and fibrils and binds plaques and reduces amyloid in vivo. Journal of Biological Chemistry, published online ahead of print December 7, 2004
A copy of the full paper can be found on the Journal of Biological Chemistry Web site at

Dietary supplement helps Alzheimer’s

A three-month study of 55 elderly patients with mild or moderate Alzheimer’s found that those given EV-1, a dietary supplement containing, among other things, the putative antioxidant ingredient of red wine, showed no deterioration during the trial. The supplement is designed to interfere with a defective mitochondrial cycle thought to contribute to the metabolic disturbances associated with late onset Alzheimer’s. The Krebs tricarboxylic acid cycle is fuelled by glucose and regulates levels of reactive oxygen species in the body. EV-1 contains glucose, a compound called malate that primes or maintains the Krebs cycle, and resveratrol - the antioxidant component of red wine that is thought to soak up reactive oxygen species. More studies are needed to confirm this result.

The findings were presented in November at the annual meeting of the Society for Neuroscience (SFN) in New Orleans.

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Estrogen for Alzheimer's

Older news items (pre-2010) brought over from the old website

For women over 65, Combined Hormone Therapy increases risk of dementia

Much to the researchers’ surprise and disappointment, a four-year experiment involving 4,532 women at 39 medical centers, has found that combined hormone therapy (involving both estrogen and progestin) doubles the risk of Alzheimer's disease and other types of dementia in women who began the treatment at age 65 or older, although the risk is still small : for every 10,000 women 65 and older who take hormones, 23 of the predicted 45 cases of dementia a year, will be attributable to the hormones. The study also found that the combined hormone therapy produced no improvement in general cognitive function, and in fact had adverse effects on cognition among some women. This supports an earlier study suggesting that, while estrogen is helpful to cognitive function in postmenopausal women, the benefits can be cancelled out by progestin / progesterone. The study also confirmed previous research showing that the combination therapy increased the risk of stroke - previous research has indicated that risk factors for stroke are also risk factors for cognitive decline.

Shumaker, S.A., Legault, C., Rapp, S.R., Thal, L., Wallace, R.B., Ockene, J.K., Hendrix, S.L., Jones, B.N. III, Assaf, A.R., Jackson, R.D., Kotchen, J.M., Wassertheil-Smoller, S. & Wactawski-Wende, J. 2003. Estrogen Plus Progestin and the Incidence of Dementia and Mild Cognitive Impairment in Postmenopausal Women: The Women's Health Initiative Memory Study: A Randomized Controlled Trial. JAMA, 289, 2651-2662.

Rapp, S.R., Espeland, M.A., Shumaker, S.A., Henderson, V.W., Brunner, R.L., Manson, J.E., Gass, M.L.S., Stefanick, M.L., Lane, D.S., Hays, J., Johnson, K.C., Coker, L.H., Dailey, M. & Bowen, D. 2003. Effect of Estrogen Plus Progestin on Global Cognitive Function in Postmenopausal Women: The Women's Health Initiative Memory Study: A Randomized Controlled Trial. JAMA, 289, 2663-2672.

Wassertheil-Smoller, S., Hendrix, S., Limacher, M., Heiss, G., Kooperberg, C., Baird, A., Kotchen, T., Curb, J.D., Black, H., Rossouw, J.E., Aragaki, A., Safford, M., Stein, E., Laowattana, S. & Mysiw, W.J. 2003. Effect of Estrogen Plus Progestin on Stroke in Postmenopausal Women: The Women's Health Initiative: A Randomized Trial. JAMA, 289, 2673-2684.

Animal studies suggest why estrogen can't help after dementia has developed

Research with rats suggests that nerve cells in the brain called cholinergic neurons are needed for estrogen to help learning and memory. This suggests why starting estrogen after dementia has developed is ineffective.

Gibbs, R.B. 2002. Basal Forebrain Cholinergic Neurons Are Necessary for Estrogen to Enhance Acquisition of a Delayed Matching-to-Position T-Maze Task, Hormones and Behavior, 42(3), 245-257.

Long-term ERT in postmenopausal women with Alzheimer's may worsen memory

A study using female rats investigated the interaction of two conditions known to exist within the brains of female Alzheimer's patients: 1) the presence of chronic neuroinflammation, and 2) having too much or not enough estrogen. They found that rats who had their ovaries removed (to model the condition of post-menopausal women) performed more poorly on a water maze task when they had chronic brain inflammation OR long-term estrogen replacement therapy. Most significantly, those who had both conditions performed much more poorly – beyond what would be expected by either condition alone. That such results extend to postmenopausal women is supported by a 2000 study involving a long term, placebo-controlled study that examined the effects of estrogen replacement therapy on cognitive function in women with mild to moderate Alzheimer's. The effects of ERT were initially beneficial, but the performance of women receiving sustained ERT declined more than that of women receiving the placebo treatment. The results of these studies suggest that postmenopausal women with Alzheimer's disease who undergo long-term estrogen replacement therapy may make their memory loss worse.

Marriott, L.K., Hauss-Wegrzyniak, B., Benton, R.S., Vraniak, P.D. & Wenk, G.L. 2002. Long-Term Estrogen Therapy Worsens the Behavioral and Neuropathological Consequences of Chronic Brain Inflammation. Behavioral Neuroscience, 116 (5), 902-11.

Estrogen patch may improve memory for women with Alzheimer's

A new study suggests that an estrogen skin patch given to women with mild to moderate Alzheimer's disease can improve their memory and attention skills. The study involved only 20 women for eight weeks, and the results will need to be confirmed by a larger-scale study. Research to date has been equivocal about the effects of estrogen on women with Alzheimer's, with some finding a memory-enhancing effect, and others finding no effect. It is speculated that the type of estrogen might be critical. The present study used estradiol, a type of estrogen that has been shown to have an effect on the brain.

Asthana, S., Baker, L. D., Craft, S., Stanczyk, F. Z., Veith, R. C., Raskind, M. A., & Plymate, S. R. (2001). High-dose estradiol improves cognition for women with AD Results of a randomized study. Neurology, 57(4), 605–612. doi:10.1212/WNL.57.4.605

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Anti-hypertensive drugs

Older news items (pre-2010) brought over from the old website

Some blood pressure drugs may help protect against dementia

High blood pressure is a major contributor to the development of all types of dementia. Data from over 1000 participants in the Cardiovascular Health Study, who were free of dementia when they entered the study and who were being treated for hypertension, has revealed that those taking centrally-active ACE inhibitors (which cross the blood-brain barrier) showed significantly lower rates of mental decline. However, non-centrally active ACE inhibitors were associated with an increased risk of dementia compared to those taking other anti-hypertensive drugs. Centrally-acting ACE inhibitors include captropril (Capoten®), fosinopril (Monopril®), lisinopril (Prinivil® or Zestri®), perindopril (Aceon®), ramipril (Altace®) and trandolapril (Mavik®).

Sink, K.M. et al. 2009. Angiotensin-Converting Enzyme Inhibitors and Cognitive Decline in Older Adults With Hypertension: Results From the Cardiovascular Health Study. Archives of Internal Medicine,169 (13), 1195-1202.

Blood pressure drugs may cut risk of Alzheimer's by 40%

Analysis of more than 5 million UK medical records has revealed that those taking drugs known as angiotensin receptor blockers (ARBs), used to treat high blood pressure, had a 35-40% lower risk of developing Alzheimer's disease and similar neurodegenerative disorders. The drugs also appeared to slow the progression of Alzheimer's disease, reducing deaths, admissions to nursing homes and certain symptoms of the condition by up to 45%. The drugs were of most benefit to patients who had experienced a stroke. The most common ARBs are marketed as candesartan, losartan and irbesartan. In the next few months, the study will be repeated using US medical records of a further 3 million patients. It’s reported that the analysis has also identified other drugs that appear to prevent Alzheimer's and some that make the condition worse. A combination of ARBs with other drugs may reduce the risk of dementia by more than 50%.

The findings were presented at the international conference on Alzheimer's disease in Chicago.

Anti-hypertensive drug may help prevent and treat Alzheimer's disease

A review of more than 1,500 drugs commercially available for treatment of other disorders, to determine their potential value in treating Alzheimer's disease, identified 7 out of 55 candidate drugs commonly prescribed for the treatment of hypertension as capable of significantly preventing beta-amyloid production. Only one of these drugs — Valsartan — was shown to have a marked in vitro effect, and this drug has now been shown to reduce the severity of Alzheimer’s in genetically engineered mice.

Wang, J. et al. 2007. Valsartan lowers brain ß-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease. Journal of Clinical Investigation, 117, 3393-3402.
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Some hypertension drugs may help reduce dementia risk

Data from the Cardiovascular Health Study, a long-term study of cardiovascular risk factors that involved 5,888 people over 65 years old, has studied 1,074 participants who were free of dementia when they entered the study and who were being treated for high blood pressure. They found use of a class of high blood pressure medicines that are centrally active ACE inhibitors was associated with lower risk of cognitive decline. The benefit did not result from ACE inhibitors in general, only to those that are centrally active (which means they can cross the blood brain barrier). Centrally acting drugs include captropril (Capoten®), fosinopril (Monopril®), lisinopril (Prinivil® or Zestri®), perindopril (Aceon®), ramipril (Altace®) and trandolapril (Mavik®).

Wolozin B, Lee A, Lee A, Whitmer R, Kazis L. Use of angiotensin receptor blockers is associated with a lower incidence and progression of Alzheimer disease. Presented at: International Conference on Alzheimer’s Disease. CA, USA, 26–31 July 2008 (Abstract O1-05-05).

Hypertension drugs might help Alzheimer’s

A project to determine whether drugs that are already commercially available for treatment of other disorders might help in treating Alzheimer’s disease using in vitro methods has identified several hundred drugs as having promise in preventing beta-amyloid build-up, of which seven are commonly prescribed to treat hypertension. One drug in particular was identified as effective in blocking the accumulation of beta-amyloid in the brain and preventing the deterioration of cognitive performance: Propranololo-HCL (Inderal), a drug widely prescribed to treat high blood pressure in elderly patients. Of course, clinical trials will need to occur before this can be confirmed.

The research was reported at the American College of Neuropsychopharmacology’s (ACNP) annual conference December 3 - 7, 2006, in Hollywood, FL.

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Older news items (pre-2010) brought over from the old website

Statins may protect against memory loss

The question of whether statins protect against dementia and memory loss bounces back and forth. In the latest study — lasting 5 years and involving 1674 older adults who were dementia-free at the start of the study but were considered high risk — it was found that those who took statins (27%) were about half as likely to develop dementia as those who didn’t take them. Statins lowered the risk of dementia in all participants, but the statins had more of an impact on the group at high risk due to metabolic syndrome.

Cramer, C. et al. 2008. Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study. Neurology, 71, 344-350.

Cholesterol-lowering drugs may not prevent Alzheimer's disease

Research on the protective benefit or otherwise of taking statins has been contradictory to date. Now new results from the long-running Religious Orders Study has come down on the side of no benefit. The study found no relation between statin use and Alzheimer’s, and no association between taking statins and a slower cognitive decline among older people.

Arvanitakis, Z., Schneider, J.A., Wilson, R.S., Bienias, J.L., Kelly, J.F., Evans, D.A. & Bennett, D.A. 2008. Statins, incident Alzheimer disease, change in cognitive function, and neuropathology. Neurology, first published on January 16, 2008 as doi: doi:10.1212/01.wnl.0000288181.00826.63

Statin treatment improves spatial memory in Alzheimer's mice

Treatment with the cholesterol-lowering statin drug Simvastatin significantly improved spatial in mice genetically bred to have an Alzheimer’s-like disease. The benefits were more pronounced in males. Levels of nNOS (neuronal nitric oxide synthase) levels were significantly higher in the hippocampus and cortex of statin treated groups as compared to similar mice that did not receive statin. nNOS is responsible for the release of nitric oxide, a substance that causes dilation of the blood vessels in the brain, thus increasing blood flow.

The findings were presented April 30 at Experimental Biology 2007 in Washington, DC.

Cholesterol treatment, including statins, may slow Alzheimer's disease progression

A study following 342 Alzheimer’s patients attending a memory clinic for almost three years has found that the disease progressed significantly more slowly in patients given cholesterol lowering drugs. A larger trial will be needed to confirm the findings.

Masse, I., Bordet, R., Deplanque, D., Al Khedr, A., Richard, F., Libersa, C. & Pasquier, F. 2005. Lipid lowering agents are associated with a slower cognitive decline in Alzheimer’s disease. Journal of Neurology Neurosurgery and Psychiatry, 76, 1624-1629.

No clear-cut answers on statins as therapy for Alzheimer's disease

A study with genetically engineered mice found that those treated with simvastatin regained their ability to navigate mazes and that the drug improved performance even for the non-engineered mice in the control group.
Another study found that four different statins reduced, to varying extent, brain cells' production of a protein fragment thought to play a key role in Alzheimer's, with fluvastatin (Lescol, Novartis) being the most effective.
However, a review of all existing randomized controlled trials of statins in people without dementia (comprising over 30,000 participants) found no evidence yet that any statin protects against cognitive decline. In a second, small study of elderly people at risk for dementia, rates of brain tissue shrinkage, measured using a special MRI scan, were no different between statin users and nonusers.
New results from three, long-running population studies that assess the possible impact of statins on preventing Alzheimer's suggest that the benefit of statins in warding off dementia largely disappears if patients are followed for several years. There are a number of large-scale clinical trials underway to try and resolve this issue.

Presented at the 9th International Conference on Alzheimer's Disease and Related Disorders (ICAD), July 17-22, 2004, in Philadelphia, Pennsylvania.
Ling Li – Enhancement of Learning and Memory by Statins Beyond Alzheimer's Disease (O4-05-01, Wed., 7/21, 3-5 pm)
Richard Parsons – Statins Reduce Beta-amyloid Production but Increase its Release From the Cell (P4-362, Wed., 7/21, 12:30 pm)
Kina Hoglund – The Effect of Simvastatin Treatment on the Processing of the Amyloid Precursor Protein in Patients with Alzheimer's Disease (P4-386, Wed., 7/21, 12:30 pm)
P. Murali Doraiswamy – Statin Use and Hippocampal Volume in Subjects at Risk for Alzheimer's Disease (O1-02-08, Sun., 7/18, 4-6 pm)
John Breitner – Can statins prevent AD, or are they just prescribed less often to those with cognitive disorders? (S1-03-01, Sun., 7/18, 1:45 pm)

Cholesterol-lowering drugs shown to decrease predictor of Alzheimer's

In a recent study, cholesterol-lowering medications known as statins lowered brain cholesterol levels in Alzheimer’s patients by 21.4%. Brain cholesterol is involved in the formation of amyloid plaques. The findings from this research provide information about the safety and efficacy of a reasonable dose of a statin on the reduction of brain cholesterol, and pave the way for research to find out what effect statins have on the cognitive impairment of people with Alzheimer’s.

Vega, G.L., Weiner, M.F., Lipton, A.M., von Bergmann, K., Lütjohann, D., Moore, C. & Svetlik, D. 2003. Reduction in Levels of 24S-Hydroxycholesterol by Statin Treatment in Patients With Alzheimer Disease. Archives of Neurology, 60, 510-515.

Statins may prevent damage by Alzheimer's disease protein

Recently, the risk of developing Alzheimer's disease has been shown to be reduced in people treated with statins (cholesterol-lowering drugs). A new study has found that statins appear to block the vasoconstrictive effects of the A-beta protein (involved in Alzheimer's disease). It is perhaps the anti-inflammatory properties of these drugs (rather than their role in lowering cholesterol) that helps protect against dementia.

Paris, D., Townsend, K.P., Humphrey, J., Obregon, D.F., Yokota, K. & Mullan, M. 2002. Statins inhibit Ab-neurotoxicity in vitro and Ab-induced vasoconstriction and inflammation in rat aortae. Atherosclerosis, 161(2), 293-299.

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