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Scientists studying the strongest genetic \u200crisk factor for Alzheimer\u2019s disease say they have new clues to how it works and how its damaging effects on the brain could potentially be reversed.<\/strong><\/p>\n Doctors have long known that the brain\u2019s blood vessels deteriorate with Alzheimer\u2019s disease, particularly in people with the APOE4 gene, but the underlying mechanisms have remained unclear.<\/p>\n In fact, APOE4 damages the brain\u2019s blood vessels and promotes the buildup of abnormal proteins, researchers at the Icahn School of Medicine at Mount Sinai in New York have discovered.<\/p>\n It does so \u200bby causing pericytes, cells that normally stabilize small blood vessels, to transform into scar-forming cells that thicken the vessels and increase the accumulation of abnormal, misfolded protein clumps known as amyloid, the \u200btarget of current treatments. These conditions can compromise the flow of blood to the brain, leading to brain damage.<\/p>\n Blocking a protein called TGF-beta that is involved \u2060in tissue cell activity and repair protected the pericytes and reversed APOE4-associated cerebrovascular degeneration in mice, the researchers also discovered.<\/p>\n Their findings are reported in two separate papers in Cell, \u00a0and Cell Stem Cell.<\/p>\n \u201cDamage to the brain\u2019s blood \u200bvessels is not simply a late consequence of Alzheimer\u2019s disease; it is a biologically active process caused by APOE4 that may be reversible,\u201d Joel Blanchard, who co-authored both papers, said in a statement.<\/p>\n \u201cThese findings reveal new \u200btherapeutic targets for preserving vascular function and limiting amyloid accumulation.\u201d<\/p>\n<\/div>\n