As such, the transcription factor PU.1 of the risk factor SPI1/CELF1 locus was detected as the gene within this locus with the highest association with AD age of onset and to have cis-regulatory, epigenetic-regulated elements in genes as CD33, MS4A4A, and TREM2, explaining the strong link between SPI1/PU.1, myeloid cells and AD [155]. Here, TREM2 is linked to Alzheimer disease.