Alzheimer’s disease (AD) is the leading cause of dementia and is strongly influenced by genetics. There are two main genetic forms of AD: a rare early-onset type caused by single gene mutations, and a much more common late-onset type that develops later in life due to the combined effects of many common genetic differences. One of the biggest genetic risk factors for late-onset AD is the APOE gene, especially the ε4 version (APOE4). Another important gene is ABCA7, which, like APOE, helps control fat (lipid) balance in the brain and may affect how harmful protein build-ups, like amyloid plaques, are managed. ABCA7 gene variant that increases the risk of developing AD may change how the gene works, but its exact role in AD is still unclear. This study looks at how a specific ABCA7 variant affects different brain cell types — including neurons, support cells (astrocytes), and immune cells (microglia) — and how it interacts with different versions of the APOE gene. Using advanced lab-grown human brain cell models, we found that a specific ABCA7 variant changes how cells behave in ways that depend on which APOE version is present. We believe this ABCA7 variant may disrupt fat metabolism in the brain and contribute to AD in a way that depends on the type of brain cell and the person’s APOE genotype. Understanding how these gene changes interact may lead to better ways to diagnose and treat Alzheimer’s through personalized medicine.
