amyloid beta

Higher blood pressure linked to greater brain damage in older adults

  • A clinical trial found that hypertensive older adults who took medication to keep their systolic blood pressure around 130 showed markedly fewer white matter lesions than those maintaining a level of 145.
  • A large, long-running study found that higher blood pressiure was linked to more brain lesions and more tau tangles.
  • A long-running study found that both higher amyloid-beta levels and higher vascular risk were linked to faster cognitive decline, with the factors interacting to be worse than additive.

Lowering blood pressure prevents worsening brain damage in elderly

A clinical trial involving 199 hypertensive older adults (average age 81) found that those who took medicine to keep their 24-hour systolic blood pressure around 130 mm Hg for three years showed 40% less accumulation of white matter lesions compared with those taking medicine to maintain a systolic blood pressure around 145 mm Hg.

60% of the patients maintained their target blood pressure throughout the full three years, and data from these alone showed an even bigger difference in number of brain lesions.

The study used around-the-clock ambulatory blood pressure monitors, which measured participants' blood pressure during all activities of daily living.

Participants had an average systolic blood pressure around 150 mm Hg at the beginning of the trial.

The research was presented at the American College of Cardiology's 68th Annual Scientific Session.

https://www.eurekalert.org/pub_releases/2019-03/acoc-lbp031819.php

Brain lesions linked to higher blood pressure in older adults

A long-running study tracking 1,288 older adults (65+) until their deaths found that the risk and number of brain lesions increased with higher blood pressure. High blood pressure was also linked to increased risk of protein tangles in the brain.

Two-thirds of the subjects had high blood pressure, while about half had one or more brain infarcts. Those with an upper blood pressure of 147 had a 46% higher chance of having one or more lesions.

https://www.the-scientist.com/news-opinion/higher-blood-pressure-has-links-to-brain-lesions-in-older-adults-64495

Vascular risk interacts with amyloid levels to increase age-related cognitive decline

Data from 223 participants in the Harvard Aging Brain Study found that both elevated brain amyloid levels and higher vascular risk were associated with more rapid cognitive decline, with the most rapid changes seen in those with both factors. The interaction between the two factors appears to be synergistic rather than simply additive — that is, the interaction between vascular factors and amyloid burden produces more risk than would be predicted from simply adding the two together.

https://www.eurekalert.org/pub_releases/2018-05/mgh-vri052118.php

Reference: 

Arvanitakis, Z., Capuano, A. W., Lamar, M., Shah, R. C., Barnes, L. L., Bennett, D. A., & Schneider, J. A. (2018). Late-life blood pressure association with cerebrovascular and Alzheimer disease pathology. Neurology, 91(6), e517. https://doi.org/10.1212/WNL.0000000000005951

[4499] Rabin, J. S., Schultz A. P., Hedden T., Viswanathan A., Marshall G. A., Kilpatrick E., et al.
(2018).  Interactive Associations of Vascular Risk and β-Amyloid Burden With Cognitive Decline in Clinically Normal Elderly Individuals: Findings From the Harvard Aging Brain Study.
JAMA Neurology. 75(9), 1124 - 1131.

Topics: 

tags development: 

tags problems: 

Lymphatic vessels critical to a healthy brain

  • Lymphatic vessels surround the brain and are vital to its ability to manage waste.
  • A mouse study has found that improvements to the flow of waste from brain to lymph nodes dramatically improved their cognition, while obstructing the lymphatic vessels increased the level of amyloid-beta plaques.

Although first reported in 1816, the fact that the brain is surrounded by lymphatic vessels, which connect the brain and the immune system, was only rediscovered in 2015.

Lymphatic vessels are part of the body's circulatory system. In most of the body they run alongside blood vessels. They transport lymph, a colorless fluid containing immune cells and waste, to the lymph nodes. Blood vessels deliver white blood cells to an organ and the lymphatic system removes the cells and recirculates them through the body. The process helps the immune system detect whether an organ is under attack from bacteria or viruses or has been injured.

Since then, brain scans have indicated that our brains drain some waste out through lymphatic vessels, and could act as a pipeline between the brain and the immune system.

More recent research suggests the vessels are vital to the brain's ability to cleanse itself. When a compound was used to improve the flow of waste from the brain to the lymph nodes in the neck of aged mice, their ability to learn and remember improved dramatically.

Moreover, obstructing the vessels in mice worsened the accumulation of harmful amyloid plaques in the brain.

https://www.eurekalert.org/pub_releases/2018-07/uovh-bdc072518.php

https://www.eurekalert.org/pub_releases/2017-10/nion-nru100317.php

Reference: 

[4498] Da Mesquita, S., Louveau A., Vaccari A., Smirnov I., R. Cornelison C., Kingsmore K. M., et al.
(2018).  Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease.
Nature. 560(7717), 185 - 191.

Absinta, Ha et al. Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI, October 3, 2017, eLife: 10.7554/eLife.29738

Source: 

Topics: 

tags problems: 

Green tea compound reverses Alzheimer's-like symptoms in mice

  • Compounds found in green tea and carrots reversed Alzheimer's-like symptoms in mice.

A diet containing compounds found in green tea and carrots reversed Alzheimer's-like symptoms in mice genetically programmed to develop the disease. The two compounds were EGCG (epigallocatechin-3-gallate), a key ingredient in green tea, and FA (ferulic acid), which is found in carrots, tomatoes, rice, wheat and oats.

After three months, the treatment completely restored working memory deficits seen in the Alzheimer's mice. The compounds appeared to help prevent amyloid precursor proteins from breaking up into amyloid beta, as well as reduce neuroinflammation and oxidative stress in the brain.

The amount of EGCG and FA was no more than could be gained from an appropriate diet.

https://www.eurekalert.org/pub_releases/2019-03/uosc-asr030619.php

Reference: 

Source: 

Topics: 

tags lifestyle: 

tags problems: 

Canola oil impairs brains of Alzheimer's mice; olive oil helps them

  • Studies involving genetically engineered mice found that canola oil was linked to worse cognition, more amyloid plaques, and greater synapse loss, while extra-virgin olive oil was linked to fewer plaques, less inflammation, and better memory.

A mouse study has found that canola oil in the diet was associated with worsened memory, worsened learning ability, and weight gain in Alzheimer's mice.

Canola oil-treated animals also had greatly reduced levels of amyloid beta 1-40 (the “good” version), leading to more amyloid-beta plaques (made from amyloid beta 1-42), and a significant decrease in synapses.

The mice were given the equivalent of about two tablespoons of canola oil daily. The mice began their enriched diet at 6 months of age, before they developed any signs of Alzheimer's.

A previous study by the same researchers found that Alzheimer’s mice fed a diet enriched with extra-virgin olive oil had reduced levels of amyloid plaques and phosphorylated tau and experienced memory improvement.

Moreover, olive oil reduced inflammation in the brain, improved synaptic integrity, and dramatically increased levels of autophagy (the process by which waste products from cells are cleared away).

https://www.eurekalert.org/pub_releases/2017-12/tuhs-trc120617.php

https://www.eurekalert.org/pub_releases/2017-06/tuhs-tse061917.php

Reference: 

Source: 

Topics: 

tags lifestyle: 

tags problems: 

Why gum disease increases dementia risk

  • A very large Korean study found older adults with chronic periodontitis had a 6% higher risk for dementia.
  • Two animal studies found that the bacteria involved in gum disease increases amyloid-beta, brain inflammation, and neuron death.

Periodontitis raises dementia risk

A 10-year South Korean study using data from 262,349 older adults (50+) has found that those with chronic periodontitis had a 6% higher risk for dementia than did people without periodontitis. This connection was true despite behaviors such as smoking, consuming alcohol, and remaining physically active.

https://www.eurekalert.org/pub_releases/2019-03/ags-pmr031519.php

Gum disease link to Alzheimer's explained

Gum disease has been linked to Alzheimer's as a risk factor, and now an animal study provides evidence that Porphyromonas gingivalis (Pg), the bacterium associated with chronic gum disease, colonizes the brain and increases production of amyloid beta.

Moreover, the bacterium's toxic enzymes (gingipains) have been found in the neurons of patients with Alzheimer’s. Gingipain levels were associated with two markers: tau, and ubiquitin (a protein tag that marks damaged proteins).

When molecule therapies targeting Pg gingipains were applied, there was reduced bacterial load of an established Pg brain infection, blocked amyloid-beta production, reduced neuroinflammation and protected neurons in the hippocampus.

Around half the population are said to have this bacteria in some form, and around 10% of those with the bacteria will develop serious gum disease, loose teeth, and have an increased risk of developing Alzheimer´s disease.

https://www.eurekalert.org/pub_releases/2019-01/uol-nsd012319.php

https://www.eurekalert.org/pub_releases/2019-06/tuob-byt060319.php

Mouse study links periodontal disease bacteria to greater amyloid plaques, brain inflammation, neuron death

A mouse study found that long-term exposure to periodontal disease bacteria resulted in significantly higher amounts of amyloid beta plaque, more brain inflammation and fewer intact neurons. It’s important to note that the mice used in the study were not genetically engineered to develop Alzheimer's.

https://www.eurekalert.org/pub_releases/2018-10/uoia-pdb100318.php

Reference: 

Source: 

Topics: 

tags problems: 

Anxiety linked to rising amyloid-beta levels

  • A study found an association in healthy older adults between higher amyloid beta levels and worsening anxiety.

Data from the Harvard Aging Brain Study found that higher amyloid beta levels were associated with increasing anxiety symptoms in cognitively normal older adults. The results suggest that worsening anxious-depressive symptoms may be an early predictor of elevated amyloid beta levels.

The study involved 270 cognitively healthy older adults (62-90). For five years, participants were annually assessed for depression, apathy-anhedonia, dysphoria, and anxiety.

https://www.eurekalert.org/pub_releases/2018-01/bawh-aa011118.php

Reference: 

Donovan et al. 2017. Longitudinal Association of Amyloid Beta and Anxious-Depressive Symptoms in Cognitively Normal Older Adults. The American Journal of Psychiatry DOI: 10.1176/appi.ajp.2017.17040442

Source: 

Topics: 

tags memworks: 

tags problems: 

Impaired waste management in the brain a cause of Alzheimer's?

  • A mouse study has shown that, as cells age, their ability to remove damaged proteins and structures (autophagy) declines, due to a decrease in the cell components (autophagosomes) that collect the damaged proteins.
  • A study found that the process of breaking down defective mitochondria and recycling the components (mitophagy) is impaired in those with Alzheimer's.
  • Microglia clear damage by engulfing the damaged matter then releasing it inside exosomes, which can be absorbed by other cells. Studies have now shown that these exosomes, designed to transmit information, can also spread harmful tau & amyloid-beta protein.
  • A mouse study has shown how amyloid plaques lead to tau tangles, and that weakened microglia facilitate this. It also links weak microglia to the risky variant of the TREM2 gene.
  • However, the common TREM2 variant is linked to faster plaque growth at later stages.
  • TREM2 appears to modify the way immune cells respond to tau tangles.
  • Another mouse study found that overactive microglia (achieved by turning off another gene) were linked to both better removal of amyloid-beta, and loss of synapses. This may help explain why reducing amyloid plaques often fails to improve cognition.

Aging linked to impaired garbage collection in the brain

A mouse study has shown that, as cells age, their ability to remove damaged proteins and structures declines.

The process of waste management, called autophagy, involves a component within the cell (an autophagosome) engulfing misfolded proteins or damaged structures (putting them in a garbage bag, essentially). The autophagosome then fuses with a second cellular structure, called a lysosome, that contains the enzymes needed to breakdown the garbage, allowing the components to be recycled and reused.

It’s thought that this decline in autophagy makes neurons more vulnerable to genetic or environmental risks.

The mouse study found that aging brought a significant decrease in the number of autophagosomes produced, along with pronounced defects in their structure.

However, activating the protein WIPI2B restored autophagosome formation.

https://www.eurekalert.org/pub_releases/2019-07/uops-tot071919.php

Breakdown in cleaning process in mitochondria linked to Alzheimer's

A cleaning process in brain cells called mitophagy breaks down defective mitochondria and reuses the proteins that they consist of. When the process breaks down, defective mitochondria accumulate in brain cells.

Research has now found that this is markedly present in cells from both humans and animals with Alzheimer's. Moreover, when active substances targeted at the cleaning process were tried in live animals, their Alzheimer's symptoms almost disappeared.

https://www.eurekalert.org/pub_releases/2019-02/uoct-oc021419.php

Microglia may spread toxic tau during early Alzheimer's

A 2015 study found how toxic tau fibrils spread during the early stages of Alzheimer's disease. Apparently the fibrils (accumulations of tau proteins) can be carried from one neuron to another by microglia.

Microglia act as the brain's immune cells, in which role they identify and clear damage and infection. They clear damage by first engulfing dead cells, debris, inactive synapses or even unhealthy neurons, then releasing nano-scale particles called exosomes, which can be absorbed by other cells.

It used to be thought that exosomes simply help the cell to get rid of waste products. It now appears that cells throughout the body use exosomes to transmit information. This requires them to contain both proteins and genetic material, which other cells can absorb. Hence their ability to spread tau protein, and hence, it now seems, their ability to also transport amyloid-beta.

http://www.eurekalert.org/pub_releases/2015-10/bumc-rdr100515.php

https://www.eurekalert.org/pub_releases/2018-06/lu-nmb061318.php

Microglia link Alzheimer’s amyloid and tau

Amyloid plaques and tau tangles are key biomarkers for Alzheimer’s, but research indicates that it is the tau tangles that are the real problem — the main problem with amyloid plaques is that they lead to tau tangles. A new study indicates how that happens.

A mouse study modified the TREM2 genes, which affect the health of microglia. So some mice carried the common variant of the gene, meaning that their microglia were fully functional, and some carried the risky variant, or no gene at all.

When seeded with tau protein from Alzheimer’s patients, those brains with weakened microglia produced more tau tangle-like structures near the amyloid plaques than in mice with functional microglia.

It was also revealed that microglia normally form a cap over amyloid plaques that limits their toxicity to nearby neurons. When the microglia failed to do that, neurons suffered more damage, creating an environment that fostered the formation of tau tangle-like lesions.

The findings were supported by the finding that humans with TREM2 mutations who died with Alzheimer’s had more tau tangle-like structures near their amyloid plaques than people who died with Alzheimer’s but didn’t have the risky gene.

https://www.futurity.org/alzheimers-disease-amyloid-plaques-tau-2095692/

https://www.eurekalert.org/pub_releases/2019-06/wuso-aml062319.php

However, it should be noted that in more advanced stages of Alzheimer’s, mice with the common TREM2 variant showed faster plaque growth. This appears to be linked to the gene inducing microglia to produce ApoE, which enhances aggregate formation.

The finding adds to evidence that Alzheimer's treatment has to take into account the stage at which the disease is at.

https://www.eurekalert.org/pub_releases/2019-01/d-gc-dic010819.php

Another study that modified the TREM2 gene in mice found that the difference between those with the gene and those without was not in the amount of tau tangles, but rather in the way their immune cells responded to the tau tangles. The microglia in mice with TREM2 were active, releasing compounds that in some circumstances help fight disease, but in this case primarily injured and killed nearby neurons. The microglia in mice without TREM2 were much less active, and their neurons were relatively spared.

https://www.eurekalert.org/pub_releases/2017-10/wuso-agp100617.php

http://www.futurity.org/trem2-alzheimers-disease-1573272/

Overactive microglia have multiple effects

A study found that, if the gene for the TDP-43 protein was turned off in microglia, its activity increased, and amyloid-beta was removed very efficiently. However, when TDP-43 was switched off in microglia in mice, it didn’t just get better at removing amyloid-beta, but also led to a significant loss of synapses.

Clearly, dysfunction of microglia is a complicated business, and it’s suggested that such dysfunction may be one reason why many Alzheimer's medications reduce amyloid plaques but fail to improve cognition.

https://www.eurekalert.org/pub_releases/2017-06/uoz-osc062917.php

Classifying brain microglia

Microglia come in many forms. A survey of brain microglia has classified microglia into at least nine distinct groups, including some types never detected in the past. Some types appeared almost exclusively in the embryonic or newborn stages, others only after injury.

One group tended to cluster near the brain's developing white matter. Another appears to be very inflammatory compared with other microglia, and has been found in people with MS.

Microglia were most diverse early in brain development, in the aged brain and in disease.

https://www.eurekalert.org/pub_releases/2018-12/bch-cbm120518.php

Reference: 

[4447] Stavoe, A. K. H., Gopal P. P., Gubas A., Tooze S. A., & Holzbaur E. L. F.
(2019).  Expression of WIPI2B counteracts age-related decline in autophagosome biogenesis in neurons.
(Dikic, I., Marder E., & Hurley J. H., Ed.).eLife. 8, e44219.

[4448] Fang, E. F., Hou Y., Palikaras K., Adriaanse B. A., Kerr J. S., Yang B., et al.
(2019).  Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease.
Nature Neuroscience. 22(3), 401 - 412.

Maitrayee Sardar Sinha, Anna Ansell-Schultz, Livia Civitelli, Camilla Hildesjö, Max Larsson, Lars Lannfelt, Martin Ingelsson and Martin Hallbeck, Alzheimer disease pathology propagation by exosomes containing toxic amyloid-beta oligomers, Acta Neuropathologica, published online 13 June 2018, doi: 10.1007/s00401-018-1868-1 https://link.springer.com/article/10.1007/s00401-018-1868-1

[4451] Leyns, C. E. G., Gratuze M., Narasimhan S., Jain N., Koscal L. J., Jiang H., et al.
(2019).  TREM2 function impedes tau seeding in neuritic plaques.
Nature Neuroscience. 22(8), 1217 - 1222.

Parhizkar et al. (2019): "Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE", Nature Neuroscience, DOI: 10.1038/s41593-018-0296-9

Leyns C, Ulrich J, Finn M, Stewart F, Koscal L, Remolina Serrano J, Robinson G, Anderson E, Colonna M, Holtzman DM. TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy. Proceedings of the National Academy of Sciences. Week of Oct. 9, 2017.

[4452] Paolicelli, R. C., Jawaid A., Henstridge C. M., Valeri A., Merlini M., Robinson J. L., et al.
(2017).  TDP-43 Depletion in Microglia Promotes Amyloid Clearance but Also Induces Synapse Loss.
Neuron. 95(2), 297 - 308.e6.

[4464] Hammond, T. R., Dufort C., Dissing-Olesen L., Giera S., Young A., Wysoker A., et al.
(2019).  Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes.
Immunity. 50(1), 253 - 271.e6.

Topics: 

tags problems: 

Lower tau levels may obscure early Alzheimer’s in black patients

  • Two large studies show an association between the Alzheimer's protein tau and the Alzheimer's gene APOE4, but the association varies across race and gender.

Data from 1,215 older adults, of whom 173 (14%) were African-American, has found that, although brain scans showed no significant differences between black and white participants, cerebrospinal fluid (CSF) showed significantly lower levels of the brain protein tau in African-Americans.

While both groups showed the same (expected) pattern of higher tau levels being associated with greater chance of cognitive impairment, the absolute amounts of tau protein were consistently lower in African-Americans.

However, when APOE status was taken into account, it was found that those who held the low-risk variants of the “Alzheimer’s gene” had similar levels of tau, regardless of race. It was only African-Americans with the APOE4 gene variant that showed lower levels of tau.

This suggests that the APOE4 risk factor has different effects in African-Americans compared to non-Hispanic white Americans, and points to the need for more investigation into how Alzheimer’s develops in various populations.

Interestingly, another study, using data from 1798 patients (of whom 1690 were white), found that there was a strong gender difference in the association between APOE status and tau levels in the CSF.

Previous research has shown that the link between APOE4 and Alzheimer's is stronger in women than men. This study points to a connection with tau levels, as there was no gender difference in the association between APOE and amyloid-beta levels, amyloid plaques, or tau tangles.

https://www.futurity.org/alzheimers-disease-black-patients-1951502/

Reference: 

Morris JC, Schindler SE, McCue LM, et al. Assessment of Racial Disparities in Biomarkers for Alzheimer Disease. JAMA Neurol. Published online January 07, 2019. doi:10.1001/jamaneurol.2018.4249

Hohman TJ, Dumitrescu L, Barnes LL, et al. Sex-Specific Association of Apolipoprotein E With Cerebrospinal Fluid Levels of Tau. JAMA Neurol. 2018;75(8):989–998. doi:10.1001/jamaneurol.2018.0821

 

Topics: 

tags development: 

tags memworks: 

tags problems: 

More evidence that stress increases risk of Alzheimer's

  • A stress hormone has been found to be associated with more amyloid-beta protein, in mice and human neurons.
  • The finding helps explain why stress is a risk factor for Alzheimer's.
  • A previous 38-year study supports this with the finding that women who scored highly in "neuroticism" in middle age, had a greater chance of later developing Alzheimer's.
  • This link was largely accounted for by chronic stress experienced by these women over the four decades.

A study involving both mice and human cells adds to evidence that stress is a risk factor for Alzheimer's.

The study found that mice who were subjected to acute stress had more amyloid-beta protein in their brains than a control group. Moreover, they had more of a specific form of the protein, one that has a particularly pernicious role in the development of Alzheimer's disease.

When human neurons were treated with the stress hormone corticotrophin releasing factor (CRF), there was also a significant increase in the amyloid proteins.

It appears that CRF causes the enzyme gamma secretase to increase its activity. This produces more amyloid-beta.

The finding supports the idea that reducing stress is one part of reducing your risk of developing Alzheimer's.

A neurotic personality increases the risk of Alzheimer's disease

An interesting study last year supports this.

The study, involving 800 women who were followed up some 40 years after taking a personality test, found that women who scored highly in "neuroticism" in middle age, have a greater chance of later developing Alzheimer's. People who have a tendency to neuroticism are more readily worried, distressed, and experience mood swings. They often have difficulty in managing stress.

The women, aged 38 to 54, were first tested in 1968, with subsequent examinations in 1974, 1980, 1992, 2000, and 2005. Neuroticism and extraversion were assessed in 1968 using the Eysenck Personality Inventory. The women were asked whether they had experienced long periods of high stress at each follow-up.

Over the 38 years, 153 developed dementia (19%), of whom 104 were diagnosed with Alzheimer's (13% of total; 68% of those with dementia).

A greater degree of neuroticism in midlife was associated with a higher risk of Alzheimer's and long-standing stress. This distress accounted for a lot of the link between neuroticism and Alzheimer's.

Extraversion, while associated with less chronic stress, didn't affect Alzheimer's risk. However, high neuroticism/low extraversion (shy women who are easily worried) was associated with the highest risk of Alzheimer's.

The finding supports the idea that long periods of stress increase the risk of Alzheimer's, and points to people with neurotic tendencies, who are more sensitive to stress, as being particularly vulnerable.

http://www.eurekalert.org/pub_releases/2015-09/uof-uhr091615.php

http://www.eurekalert.org/pub_releases/2014-10/uog-anp101414.php

Reference: 

Topics: 

tags development: 

tags memworks: 

tags problems: 

Pages

Subscribe to RSS - amyloid beta