Gene accessibility may explain why Alzheimer’s risk from APOE4 differs by ancestry, according to FunGen-AD-supported research

Researchers at the John P. Hussman Institute for Human Genomics at the University of Miami, Miller School of Medicine, including FunGen-AD researchers Derek Dykxhoorn, Anthony Griswold, Jeffery Vance, and Juan Young, recently published a study showing differences in chromatin accessibility between ancestries. Previously, they reported that Alzheimer’s disease (AD) brains express a significantly greater amount of APOE4 RNA if the region around APOE reflects European rather than African ancestry. To identify a mechanism that could cause this difference, they studied chromatin in astrocytes from brains of Europeans and African Americans affected by AD. They found that increased chromatin accessibility of APOE4 in astrocytes from Europeans corresponds with elevated APOE4 expression. Increased expression of APOE4 may explain why individuals with European local ancestry near APOE4 have a higher risk of developing AD than those with African local ancestry. Results of this study may inform decisions about diagnostics, clinical care, and treatment. Patient local ancestry surrounding APOE4 is important when assessing AD risk associated with APOE4 status.

The research was supported in part by FunGen-AD grant U01AG072579 and RF1AG059018 published in Alzheimer’s & Dementia here. You can read more about the research findings at the following link: