CLU, CR1 and PICALM genes associate with Alzheimer's-related senile plaques

Introduction: APOE is the strongest risk gene for sporadic Alzheimer's disease (AD) so far. Recent genome wide association studies found links for sporadic AD with CLU and CR1 involved in A beta clearance, and PICALM affecting intracellular trafficking. Methods: We investigated the associations of senile plaques (SP) and neurofibrillary tangles (NFT) with the proposed risk genes and APOE, in the Tampere Autopsy Study (TASTY) series (603 cases), a sample of the general population (0 to 97 yrs), who died out-of-hospital. Results: Age and the APOE epsilon 4 allele associated strongly with all phenotypes of SP, as expected. In age and APOE epsilon 4 adjusted analyses, compared to the most common homozygous genotype, burnt out SP were more common among carriers of the C-allele of CLU, whereas the T-allele of PICALM and C-allele of CR1 were linked with lower SP coverage. We found no significant associations between any of the genetic variants and NFT. Conclusions: Marginal effects from CLU, CR1 and PICALM suggest that these genes have minimal effects on the development of AD lesions.