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Amyloid-β Causes Pericyte Dysfunction and Reduced Blood Flow in the Aging Brain


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Posted 25 June 2019 - 10:22 AM


The brain is an energy-hungry organ, and the supply of oxygen and nutrients to brain tissue is vital to its function. This is one of the reasons why cardiovascular disease contributes to neurodegeneration. Researchers know that cells that wrap small blood vessels in the brain, called pericytes, tend to become dysfunctional or die in later life, another of the cellular casualties of the damage of aging. This causes greater constriction of the blood vessels, reducing the blood flow to tissues. Researchers here provide evidence for this to be a consequence of the aggregation of amyloid-β, characteristic of the early stages of Alzheimer's disease. This is an intriguing addition to what is known of the issues caused by protein aggregation in neurodegenerative conditions.

A new study looked at the role of pericytes, cells wrapped around capillaries that have the ability to contract and regulate blood flow. Researchers examined capillaries in Alzheimer's-affected human brain tissue and in mice bred to develop Alzheimer's pathology, and found that they were squeezed by pericytes. They also applied amyloid beta protein (which accumulates in the brains of people with Alzheimer's) to slices of healthy brain tissue, and found that the capillaries were squeezed as a result. They calculated that the constriction was severe enough to halve blood flow, which is comparable to the decrease in blood flow found in parts of the brain affected by Alzheimer's.

"Our study has, for the first time, identified the underlying mechanism behind the reduction of brain blood flow in Alzheimer's disease. Since reduced blood flow is the first clinically detectable sign of Alzheimer's, our research generates new leads for possible treatments in the early phase of the disease. Damage to synapses and neurons in Alzheimer's is usually attributed to the actions of amyloid and tau proteins accumulating in the brain. Our research raises the question of what fraction of the damage is a consequence of the decrease in energy supply that amyloid produces by constricting the brain's finer blood vessels. In clinical trials, drugs that clear amyloid beta from the brain have not succeeded in slowing mental decline at a relatively late phase of the disease. We now have a new avenue for therapies intervening at an earlier stage."

Link: https://www.ucl.ac.u...line-alzheimers


View the full article at FightAging




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