TREM2 and Alzheimer disease: Furthermore, single-nucleotide polymorphisms (SNPs) within the MS4A gene cluster, such as rs1582763, are associated with increased levels of soluble TREM2 (sTREM2) in cerebrospinal fluid; remarkably, sTREM2 can reduce AD risk and delay AD onset; conversely, the rs6591561 locus is linked to decreased sTREM2 levels, leading to increased AD risk (30).