TREM2 mediates microglial clearance of lipoprotein–Aβ complexes. AD-associated TREM2 mutations impair this function, linking APOE-CLU-TREM2 risk network to impaired Aβ clearance.of the TREM2-APOE-CLU genetic risk network, and offering new targets for immunometabolic therapy in AD. This evidence concerns the gene CLU and Alzheimer disease.