A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease

Abstract summary

Showed that non-coding Alzheimer's disease risk variants at the SPI1 (PU.1) locus delay PU.1 expression and reduce microglial function. Lower PU.1 activity is associated with later disease onset. PU.1 is a master transcription factor for myeloid cell identity and regulates expression of many AD risk genes including TREM2, CD33, and MS4A family members.

Evidence labels

Therapeutic relevance

Identifies PU.1 as a master regulator of microglial AD risk gene expression; modulating PU.1 activity is a potential upstream therapeutic approach.