A Possible Feedback Loop Between Abnormal Brain Activity and Neuroinflammation in Alzheimer's Disease

Researchers here put forward an interesting view of the progression of Alzheimer's disease, in which abnormal modes of brain activity are part of a feedback loop that between inflammation and pathological protein aggregation. Evidence strongly suggests that chronic inflammation in brain tissue is an important component of neurodegenerative conditions, and the aggregation of altered proteins such as tau is both caused by inflammation and contributes to it. It is interesting to see that view expanded out to encompass the neural activity of the brain as a part of the downward spiral of interacting dysfunctions.

Scientists have known for a while that Alzheimer's disease is associated with chronic inflammation in the brain. A driver of this inflammation appears to be the accumulation of amyloid proteins in the form of "plaques," a neuropathological hallmark of the illness. In a new study, researchers identified non-convulsive epileptic activity as another critical driver of chronic brain inflammation in an Alzheimer's-related mouse model. This subtle type of epileptic activity also occurs in a substantial proportion of people with Alzheimer's disease and can be a predictor of faster cognitive decline in the patients. "One way this subclinical epileptic activity may accelerate cognitive decline is by promoting brain inflammation."

Researchers discovered that, when they reduced epileptic activity in the mouse brain, one of the inflammatory factors most affected was TREM2, which is produced by microglia, the brain's resident immune cells. People with genetic variants of TREM2 are two to four times more likely to develop Alzheimer's disease than people with normal TREM2, but scientists are still trying to decipher the precise roles this molecule plays in health and disease.

The scientists first showed that TREM2 was increased in brains of mice with amyloid plaques, but reduced after suppression of their epileptic activity. To find out why, they examined whether TREM2 affects the susceptibility of mice to low doses of a drug that can cause epileptic activity. Mice with reduced levels of TREM2 showed more epileptic activity in response to this drug than mice with normal TREM2 levels, suggesting that TREM2 helps microglia suppress abnormal neuronal activities.

"TREM2 has been primarily studied in relation to pathological hallmarks of Alzheimer's disease such as plaques and tangles. Here, we found that this molecule also has a role in regulating neural network functions. The genetic variants of TREM2 that increase the risk for Alzheimer's disease appear to impair its function. If TREM2 doesn't work properly, it could be harder for immune cells to suppress neuronal hyperexcitability, which in turn might contribute to the development of Alzheimer's disease and accelerate cognitive decline."

Link: https://gladstone.org/news/alzheimers-disease-may-cause-vicious-circle-between-brain-network-and-immune-cell-dysfunctions


Very interesting. The mainstream view is that no matter what brain activity is happening as long as you get enough rest it doesn't matter.

On the other hand, a physical activity could be quite damaging in some cases (like damaging the back/kness/tendons)

Posted by: Cuberat at November 3rd, 2021 9:50 AM
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