Alzheimer's & Other Dementias

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New mechanism adds to understanding of Alzheimer's causes

Age-related changes in gene enhancers have been linked to faster cognitive decline in Alzheimer's brains.

New findings identify a mechanism that accelerates aging in the brain and gives rise to Alzheimer's disease.

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

Inflammation linked to brain health

Study indicates APOE4 carriers are only at greater Alzheimer's risk if they have chronic inflammation.
Large study finds increasing inflammation linked to more white matter damage.
Common causes of chronic inflammation include cardiovascular disease, heart failure, diabetes, high blood pressure and infections.

Link found between chronic inflammation and Alzheimer's gene risk

Why APOE4 gene increases Alzheimer's risk

Synapses in Alzheimer's brains found to be clogged with clusterin and amyloid-beta proteins, and APOE4 carriers had more protein clumps than those without the gene variant.
APOE4 decreases activity in hippocampus that is critical for memory consolidation.
Study of Amazonian hunter-gatherers show APOE4 gene can provide benefits when exposure to parasites is high.

Alzheimer's gene linked to damage to brain connections

A study has found that synapses in people who had died with Alzheimer's contained clumps of clusterin and clumps of amyloid beta. These protein clumps may be damaging the links between neurons.

Researchers classify Alzheimer's patients in 6 subgroups

More evidence that Alzheimer's disease is not a single disease with a single cause and single pathway comes from a large study classifying patients into 6 groups, only two of which showed strong genetic association.
Another study using post-mortem brain tissue found that different genes were associated with different types of brain damage.

A study involving 4,050 people with late-onset Alzheimer's disease (mean age 80) has classified them into six groups based on their cognitive functioning at the time of diagnosis. A genetic study found two of the groups showed strong genetic associations.

Genes linked to Alzheimer's

Very large study finds 5 new genes linked to increased Alzheimer's risk.
A rare gene variant that protects APOE4 gene carriers from getting Alzheimer's has been identified.
Two large surveys found that verbal recall score was significantly affected by TOMM40 genotype. TOMM40 is adjacent to APOE on their chromosome.
A study found that TOMM40's effect on Alzheimer's depends on parental history.
Data from three very large studies has produced a tool for assessing an individual's genetic risk for developing Alzheimer's, based on 31 genetic markers.
A small study found that, of the top 9 genes that affect Alzheimer's risk, excluding the APOE gene, only 2 affect brain atrophy.
A new gene variant that is associated with greater amyloid plaque than APOE4 has been identified.

Five new risk genes for Alzheimer's disease

Genetic data from more than 94,000 individuals has revealed five new risk genes for Alzheimer's disease, and confirmed 20 known others. The new genes are: IQCK, ACE, ADAM10, ADAMTS1 and WWOX.

Gender differences in Alzheimer's disease may be linked to tau spread

Brain scans suggest that tau proteins may spread more rapidly through women’s brains, increasing Alzheimer's risk and speeding its progression.

Accumulating evidence suggests that tau spreads through brain tissue like an infection, traveling from

Alzheimer's gene linked to worse cognition

Review found APOE4 carriers scored lower on IQ tests during childhood and adolescence.
A large internet-based study found that adults with a first-degree relative with Alzheimer's performed worse on a paired-learning task.

Alzheimer's gene affects IQ from childhood

Analysis of some old longitudinal studies has found that those carrying the APOE4 gene scored lower on IQ tests during childhood and adolescence. The effect was much stronger in girls than in boys, and affected reasoning most strongly.

Genes help explain why Alzheimer’s drugs have been so unsuccessful

A gene present in 75% of the human population may be a key reason why a class of drugs for Alzheimer’s disease seem promising in animal studies but fail in human studies.
Cell study finds APOE4 protein is slightly misshapen, causing it to break down into disease-causing fragments. But APOE4 doesn't affect amyloid-beta in mice.

Data from a ten-year study involving 345 Alzheimer's patients has found that

Poor sleep drives Alzheimer’s progression

Getting a good night’s sleep is given greater importance with the discovery that sleep deprivation appears to rapidly increase the spread of tau tangles.

Poor sleep has been associated with the development of Alzheimer's disease, and this has been thought to be in part because the protein amyloid beta increases with sleep deprivation. A new study explains more.

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