Alzheimer’s risk gene APOE4 may have a reversible weakness

The Alzheimer’s risk gene APOE4 may actively damage brain blood vessels and sabotage the cellular systems that remove harmful proteins. Researchers were able to reverse some of these effects in experiments, revealing promising new targets for Alzheimer’s, Parkinson’s, and other neurodegenerative diseases. Mount Sinai researchers have uncovered new details about how APOE4, the strongest known genetic risk factor for Alzheimer's disease, may contribute to brain damage. Two studies published in Cell and Cell Stem Cell show that the gene can damage blood vessels in the brain and encourage the accumulation of abnormal proteins associated with neurodegenerative disease. The findings point to disease processes that may be reversible and also highlight a new human brain tissue platform derived from stem cells that could speed up the search for treatments.

Alzheimer's disease gradually damages memory, thinking, and behavior and affects more than 7 million older adults in the United States. Researchers have known for years that blood vessels in the brain deteriorate as Alzheimer's progresses, especially in people who carry APOE4. What has been less clear is why this happens and whether the vascular damage contributes directly to the disease. Because of that uncertainty, damage to the brain's circulation has often been treated as a consequence of Alzheimer's rather than as a process that could help drive