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Recent genome-wide association studies of Alzheimer's disease (AD) have identified variants in  BIN1 ,  CLU ,  CR1  and  PICALM  that show replicable association with risk for disease. We have thoroughly sampled common variation in these genes, genotyping 355 variants in over 600 individuals for whom measurements of two AD biomarkers, cerebrospinal fluid (CSF) 42 amino acid amyloid beta fragments (Aβ 42 ) and tau phosphorylated at threonine 181 (ptau 181 ), have been obtained. Association analyses were performed to determine whether variants in  BIN1, CLU, CR1  or  PICALM  are associated with changes in the CSF levels of these biomarkers. Despite adequate power to detect effects as small as a 1.05 fold difference, we have failed to detect evidence for association between SNPs in these genes and CSF Aβ 42  or ptau 181  levels in our sample. Our results suggest that these variants do not affect risk via a mechanism that results in a strong additive effect on CSF levels of Aβ 42  or ptau 181 .

Fine Mapping of Genetic Variants in BIN1, CLU, CR1 and PICALM for Association with Cerebrospinal Fluid Biomarkers for Alzheimer's Disease