The frequently reported AD GWAS risk single nucleotide polymorphisms (SNPs) of CLU, rs11136000 and rs11787077, both have a minor allele frequency of 0.38 in Caucasians and their minor alleles are less frequently observed in AD individuals than in controls with an AD risk odds ratio (OR) of 0.9 [2–7, 30–34].To better understand the disease mechanism of the AD risk locus near CLU, it is imperative to identify the AD causative variant and investigate the functional consequences of the AD risk allele in disease-relevant cell types. This evidence concerns the gene CLU and Alzheimer disease.