FunGen-AD-funded research identifies immune regulators in Alzheimer’s

FunGen-AD researcher Alison Goate was part of a team of researchers at the Icahn School of Medicine at Mount Sinai that used genetic and genomic tools to uncover new information about regulators of the macrophage transcriptomic state. These discoveries could provide therapeutic targets for modulating macrophage function in Alzheimer’s and other diseases.

Macrophages are immune cells found in fatty tissues like the brain. Resident tissue macrophages of the brain are called microglia but resemble macrophages in other tissues. Disease-associated macrophages are believed to be protective because of their role in removing lipid-rich waste derived from tissue damage. The research team aimed to identify factors that promote this waste removal activity.

“Through our analysis of single-cell datasets from multiple organs, we’ve uncovered pivotal regulators of immune cell function essential for tissue health,” said Goate. Using gene editing technology, the team confirmed that two influential genes, BHLHE40 and BHLHE41, support improved waste removal activity in the brain. The research team will continue to study this critical role of these two genes.

This research was partially supported by FunGen-AD grant U01AG058635 and published in Nature here. You can read more about the research findings at the following links: