Mount Sinai studies find APOE4 brain vessel damage may be reversible

October 1, 2026 at 09:52 AM2 min

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Mount Sinai researchers have identified how the Alzheimer's risk gene APOE4 damages brain blood vessels, showing the process may be reversible. Two studies published in Cell and Cell Stem Cell found that APOE4 transforms pericytes into scar-producing cells, promoting vascular fibrosis and amyloid buildup. Blocking TGF-β signaling restored pericyte coverage and reduced fibrosis and amyloid in aged APOE4 mice.

Key Facts

APOE4 is the strongest known genetic risk factor for Alzheimer's disease, affecting more than 7 million older adults in the United States.
The Cell study, published on September 24, built a single-cell transcriptomic atlas of blood vessels in the human brain.
APOE4 altered pericytes into myofibroblast-like cells that produce scar tissue, promoting vascular fibrosis and amyloid buildup.
Blocking TGF-β signaling restored pericyte coverage and reduced fibrosis and amyloid around blood vessels in aged APOE4 mice.

Vascular Damage Mechanism

Mount Sinai scientists combined existing datasets to build a single-cell transcriptomic atlas of blood vessels in the human brain. The resulting map showed patterns of gene activity across the different cells that create and support the brain's vascular system. The team found that APOE4 altered the behavior of pericytes, cells that normally help stabilize small blood vessels and support the blood-brain barrier. In the presence of APOE4, pericytes changed into myofibroblast-like cells that produce scar tissue. That transformation promoted vascular fibrosis and increased the buildup of amyloid around blood vessels.

Reversibility and Therapeutic Targets

The researchers found evidence that this process could be reversed. Blocking TGF-β signaling, which plays a role in communication between cells and in tissue remodeling, restored pericyte coverage while reducing fibrosis and amyloid around blood vessels. The researchers reproduced the result in aged APOE4 mice, showing that the vascular degeneration associated with APOE4 can be therapeutically reversed. Corresponding author Joel W. Blanchard, PhD, Associate Professor of Neuroscience, and Stem Cell Biology and Regenerative Medicine, at the Icahn School of Medicine at Mount Sinai, stated that damage to the brain's blood vessels is not simply a late consequence of Alzheimer's disease but a biologically active process caused by APOE4 that may be reversible.