Genetic variants of the MS4A gene cluster, and of TGFBR2 and NECTIN2 are associated with increased CSF sTREM2 and reduced AD risk (Deming et al, 2019; Wang et al, 2024), but the mechanism of how the MS4A proteins control TREM2 shedding remains to be established. This evidence concerns the gene TREM2 and Alzheimer disease.