Recently, two large, and independent genome wide association studies of late-onset Alzheimer's disease (AD) established association with the same rs11136000 variation in the clusterin (CLU) gene. In addition, one variation, rs3851179, in the phosphatidylinositol binding clathrin assembly protein (PICALM) gene and one variation, rs6656401, in the complement component (3b/4b) receptor 1 (CR) gene were associated with AD. Here, we replicate these associations with cognitive functioning in 1380 individuals from the Danish (1905) birth cohort study of the oldest old (92-93 years at intake) using measures of Mini Mental State Examination (MMSE) and a cognitive composite score. We found a significant association between the highly frequent CLU rs11136000 T allele (38%) and better performance on the cognitive composite score (p = 0.016) explaining 0.5% of the mean variation in cognitive composite score, and for men a significant association between the highly frequent PICALM rs3851179 A allele (38%). Better performance was found (p = 0.024), explaining 1.4% of the mean variation in cognitive composite score in men. These alleles correspond to the minor alleles initially found more frequent in controls than in cases of AD.
|Original language||English (US)|
|Journal||Neurobiology of Aging|
|State||Published - Mar 2011|
Bibliographical noteFunding Information:
The study was supported by US National Institute on Aging Research Grant NIA-PO1-AG08761 . The Danish Aging Research Center is supported by a grant from the VELUX Foundation and from the National Program for Research Infrastructure 2007 from the Danish Agency for Science Technology and Innovation .