A link between CLU and AD was established when elevated expression of CLU was detected in brains from patient with AD.44–46 The connection of CLU with AD was further strengthened when rs11136000, an intronic variant of CLU, was found to be associated with AD in a statistically significant manner in two independent genome-wide association studies.13,14 However, because rs11136000 is in strong linkage disequilibrium with a few other SNP variants in CLU, including rs1532278, rs9331896, and rs9331888,71–73 it remained unclear whether CLU rs11136000 is a functional variant. This evidence concerns the gene CLU and Alzheimer disease.