rs9349407

A genome-wide association study of 725 deceased subjects identified genetic susceptibility loci for Alzheimer's disease neuritic plaque pathology. Beyond APOE and CR1, the study found ABCA7 (rs3764650, p=0.03) and CD2AP (rs9349407, p=0.03) associated with increased neuritic plaque burden. Notably, a novel APP locus variant (rs2829887, p=3.3×10⁻⁶) was associated with neuritic plaques and β-amyloid load in postmortem samples and independently replicated in cognitively normal PET imaging cohorts, implicating common genetic variation in amyloid pathology at pre-symptomatic AD stages.

This comprehensive genome-wide association study examined genetic variants contributing to late-onset Alzheimer's disease (AD) in 513 African American cases and 496 controls, plus replication in 5 white cohorts. The APOE ε4 allele showed strong association (P=9.69×10⁻²³), and after adjusting for APOE, rs6859 in PVRL2 remained significantly associated (P=0.0087). The study found associations with variants in CLU, PICALM, BIN1, EPHA1, MS4A, ABCA7, and CD33, though effect directions sometimes differed from white populations. Novel associations with suggestive evidence were identified in PROX1, CNTNAP2, STK24, and other genes, though not replicated in whites.