Moreover, recent GWAS studies have demonstrated that AD-associated common and rare genetic variants are linked to genes that regulate immune processes2,65–67 including ABCA7, CLU, CR1, MS4A4E/MS4A6A, CD33, EPHA1, HLA-DRB5, HLA-DRB1, INPP5D, MEF2C, SORL1, and TREM2. Notably, several of these AD-associated genes (CD33, MS4A4E/MS4A6A, TREM2, and ABCA7) contained binding sites for the transcription factor PU.1, a central hub in the AD gene network that is critical for regulating microglial gene expression73. This evidence concerns the gene TREM2 and Alzheimer disease.