TREM2 and Alzheimer disease: Recent findings that TREM2 loss of function similarly impacts the response of both central nervous system (CNS) and peripheral macrophages to lipid overload69–71 and that the activation state of human macrophages does not have a major impact on AD heritability enrichment72 could indicate that Alzheimer’s disease-associated variants might regulate core functions of the macrophage lineage (e.g., the phagocytic clearance of apoptotic cells and other lipid-rich cellular debris).