Researchers reveal how the destruction of pericytes lead to white matter damage degeneration

Alzheimer’s-related brain changes could start at 40

In a mouse study, scientists at the University of Southern California (USC) in Los Angeles reveal how damage to pericytes — gatekeeper cells that surround the brain’s smallest blood vessels — can trigger white matter disease, which is associated with dementia. Also, the study findings suggest that these brain changes may occur as early as the age of 40.


Gatekeeper cells
The research sheds new light on how a breakdown in the brain’s vascular system predates the accumulation of toxic plaques and tangles in the brain that bring about Alzheimer’s. The research suggests an earlier target for preventing dementia and Alzheimer’s disease. Nearly 50 percent of all dementias, including Alzheimer’s, begins with the breakdown of the smallest blood vessels in the brain and their protective “gatekeeper cells,” according to the USC study.


Earlier kick off white matter disease
That catastrophe causes a communications failure called small vessel disease. Many people with that disease also have white matter disease, the wearing away of fatty myelin that allows neurons to transfer messages within the brain network. In an animal model, researchers found that brain deterioration associated with dementia may start as early 40 in humans.

“Many scientists have focused their Alzheimer’s disease research on the buildup of toxic amyloid and tau proteins in the brain, but this study and others from my lab show that the problem starts earlier — with leaky blood vessels in the brain,” said Berislav Zlokovic, senior author of the study and holder of the Mary Hayley and Selim Zilkha Chair in Alzheimer’s Disease Research at the Keck School of Medicine. “The collapse of pericytes reduces myelin and white matter structure in the brain. Vascular dysfunctions, including blood flow reduction and blood-brain barrier breakdown, kick off white matter disease.”


The study, published in Nature Medicine on Feb. 5, explains that pericytes play a critical role in white matter health and disease via fibrinogen, a protein that circulates in blood. Fibrinogen develops blood clots so wounds can heal. When gatekeeper cells are compromised, an unhealthy amount of fibrinogen slinks into the brain and causes white matter and brain structures, including axons (nerve fibers) and oligodendrocytes (cells that produce myelin), to die.



Source: USC News | February 5, 2018

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