Years before symptoms of Alzheimer’s disease occur, damaging proteins amyloid beta and tau accumulate in the brain.
Amyloid accumulates first, but tau is particularly noxious. Wherever tangles of the tau protein appear, brain tissue dies.
This can trigger confusion and memory loss, the major signs of Alzheimer’s.
Previous research has shown that the formation of amyloid plaques and tau tangles are key steps in the development of Alzheimer’s disease.
Amyloid plaques do not cause dementia. But amyloid plaques may lead to the formation of tau tangles. However, why this happens has been unclear.
In a recent study from Washington University School of Medicine in St. Louis, researchers found that the link between the two proteins may lie in the brain’s immune cells called microglia.
They found that if the immune cells falter, amyloid plaques injure nearby neurons and create a toxic environment that accelerates the formation of tau tangles.
The findings suggest that increasing the immune cells may slow or stop the tau tangles, and may help delay or prevent Alzheimer’s.
The study is published in Nature Neuroscience. One author is David Holtzman, MD, the head of the Department of Neurology.
In the study, the team examined if the immune cells microglia could be the link.
They knew that a rare mutation in a gene called TREM2 leaves people with weak and ineffective microglia, and also increases their risk of developing Alzheimer’s by twofold to fourfold.
The researchers used mice prone to developing amyloid plaques and modified in various ways their TREM2 genes to influence the activity of their microglia.
They found in mice with weakened microglia, more tau tangle-like structures formed near the amyloid plaques than in mice with functional microglia.
Further, the researchers showed that people with TREM2 mutations who died with Alzheimer’s disease had more tau tangle-like structures near their amyloid plaques than people who died with Alzheimer’s but did not carry the mutation.
The team says that in people with TREM2 mutations, tau accumulates and then spreads faster, and these patients develop problems with memory loss and thinking more quickly because they have more of those initial tau tangles.
If doctors could break that link in people who have amyloid deposition but are still cognitively healthy, it is possible to stop disease progression before people develop problems with thinking and memory.
Future work will test if powering up microglia might slow the spread of tau tangles and forestall cognitive decline.
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