A Mechanism by which Amyloid-β can Reduce Capillary Density in the Alzheimer's Brain

Aggregation of amyloid-β is a feature of the slow buildup towards Alzheimer's disease that takes place in later life, though it remains unclear as to whether this protein aggregation is a cause or a side-effect in the progression of the condition. Separately, loss of capillary density is a feature of aging in tissues throughout the body. In energy-hungry tissues such as the brain, this is a real problem, contributing to an insufficient supply of nutrients and consequent loss of function. The exact causes of this reduced capillary density are poorly understood. Here, researchers suggest that amyloid-β aggregation is one such cause, disrupting the balance of mechanisms needed to maintain capillary vessels in tissue.

Researchers have discovered a new mechanism of Alzheimer's disease that disorganises the blood vessels around amyloid plaques, one of the characteristic features of the disease. The mechanism put forward in this study is mediated by the dysfunction of a physiological process, angiogenesis. This mechanism is important during development to form the vessels of the brain and in adulthood to revert possible damage to pre-existing vessels. The study shows that Alzheimer's disease induces angiogenesis dysfunction that causes the loss of vessels instead of the formation of new ones, undoubtedly aggravating the pathology. By identifying the molecular pathways involved, new therapeutic strategies to alleviate the effects of this disease can be rationally designed.

A characteristic feature of Alzheimer's patients is the accumulation of highly toxic substances in their brains, known as senile plaques. The brain has the capacity to clean these toxic substances via transport through the blood. Thus the fact that the plaques cause the loss of the vessels constitutes a vicious circle: having fewer vessels reduces the ability to clean the brain thus allowing more toxic substances to accumulate, which in turn continue to destroy the vessels and worsen the situation. The brain consumes much of the body's oxygen and nutrients. Thus a local reduction in the supply of these substances through the blood represents an additional strain above and beyond the existing strain from the accumulation of toxic substances.

Link: https://www.eurekalert.org/pub_releases/2021-05/uos-amt053121.php

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