A new study helps explain why having ApoE4 – the gene variant most closely linked to Alzheimer’s disease – increases the risk of neurodegeneration and white matter damage. Researchers at Weill Cornell Medicine discovered that immune cells in the brain called border-associated macrophages (BAMs) are a source of ApoE4 protein and contribute to damaging blood vessels and brain tissue. The study , published Sept.
18 in Nature Neuroscience, may help scientists identify new approaches to preventing or treating Alzheimer’s disease in people who carry the ApoE4 gene and other forms of age-related brain disease. The APOE gene encodes apolipoprotein E (ApoE), which has many roles in the brain. It also has several common variants (ApoE2, ApoE3 and ApoE4), of which ApoE4 increases the risk for Alzheimer’s disease up to 12-fold.
ApoE4 also increases the risk of damage to the white matter that underlies vascular dementia, the second-most common cause of cognitive impairment after Alzheimer’s disease. However, how ApoE4 produces these damaging effects on the brain is not completely clear. “Our study points to border-associated macrophages as a critical mediator of these deleterious effects and helps us understand how ApoE4 may contribute to damaging blood vessels and brain white matter in patients with Alzheimer’s disease or other forms of age-related brain disease,” said the study’s co-senior author, Laibaik Park , associate professor of research in neuroscience at the .