The effects of the Alzheimer’s disease genetic risk factor APOE4 on the brain’s blood vessels may be reversible, according to researchers from the Icahn School of Medicine at Mount Sinai in New York. The findings of two studies have been published in the journals Cell and Cell Stem Cell.
The researchers have identified how APOE4 may damage the brain’s small blood vessels. The gene variant is associated with an increased risk of Alzheimer’s disease, but the mechanism through which it affects the vascular system has remained unclear for a long time.
The researchers found that APOE4 affects pericytes — cells that surround small blood vessels and help maintain their normal function. Under the influence of this genetic risk factor, these cells change their properties and begin to form a type of scar-like tissue. As a result, the vessel walls become thicker and their normal function is disrupted.
At the same time, amyloid accumulation increases. This abnormal protein forms deposits that are characteristic of Alzheimer’s disease. Changes in the blood vessels may also impair blood flow to the brain and contribute to further damage to neural tissue.
In experiments on mice, the researchers found that blocking the protein TGF-beta, which is involved in regulating cell repair and activity, protected pericytes from pathological changes. Moreover, this intervention reversed APOE4-associated vascular degeneration.
“Vascular damage in Alzheimer’s disease may not only be a consequence of an already established disease, but also an active process linked to the effects of APOE4. The findings point to the potentially reversible nature of these changes and may help in the search for new ways to protect the brain’s blood vessels and limit amyloid accumulation,” the researchers explained.
However, the findings were obtained in experimental models. Further research is needed to determine whether this approach could be used to treat people.
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