Scientists have uncovered how the APOE4 gene, the strongest genetic risk factor for Alzheimer’s disease, damages blood vessels in the brain, pointing to a possible way to reverse the harm.

Two studies from the Icahn School of Medicine at Mount Sinai, published in Cell and Cell Stem Cell, found that APOE4 turns pericytes, cells that support blood vessels, into scar-producing cells.

This transformation triggers vascular fibrosis and the build-up of amyloid, the toxic protein linked to Alzheimer’s. In mice, blocking a signalling pathway called TGF-beta reversed the damage.

The findings open the door to therapies that target the blood vessel damage rather than amyloid alone, a strategy many researchers believe is overdue.

Separately, a Columbia University study in the Lancet Neurology found that a blood marker called p-tau217, combined with APOE4, can predict Alzheimer’s onset three to four years in advance. Carriers of the APOE4 gene face a markedly higher risk of the disease, but not all develop it. Understanding the mechanism is seen as a key step towards prevention.