BCHE has previously been proposed as an AD risk gene.27 Butyrylcholinesterase is known to be enriched within Aβ plaques in post-mortem human AD brains,28 and its increased presence has been suggested as a critical factor in the formation of the neuritic plaques of dementia.29 The most commonly studied BCHE SNP is the K-variant (rs1803274), which is approximately 500 kb downstream of and not in LD with rs509208. The BCHE K-variant has demonstrated synergistic effects with APOE ε4 on incidence of pathologically-confirmed late-onset AD27 and on risk of progression from MCI to AD.30 Nevertheless, the present study is the first to implicate genetic variation at the BCHE locus in brain Aβ burden in humans and represents the largest reported effect for this gene on an AD-related phenotype.
