Replication of CLU, CR1, and PICALM Associations With Alzheimer Disease

Abstract

Late-onset Alzheimer disease (LOAD), a neurodegenerative condition characterized by large numbers of senile plaques and neurofibrillary tangles in the brain, is the most common cause of dementia in elderly persons. Multiple rare mutations in the APP, PSEN1, and PSEN2 genes cause an early-onset, familial form of the disease,¹ and twin studies indicate that susceptibility alleles may contribute as much as 80% to the risk of LOAD.² Until recently, however, APOE ε4 was the only allele reliably associated with increased susceptibility to LOAD.^3-5 A robust technology has emerged that permits genome-wide association studies (GWAS) of large numbers of subjects. This technology has enabled the identification of relatively weak associations that would otherwise go undetected.