Genetic study evaluating LDLR polymorphisms and Alzheimer's disease

We genotyped SNPs rs11668477, rs12983082, rs11669576, rs2738444, rs5925 and rs1433099 in 405 Finnish AD cases and 463 controls and conducted a single allele and genotypic distribution comparison and estimated the haplotype frequencies between cases and controls and evaluated the level of biomarkers in haplotype carriers. We observed that T allele of rs2738444 was overrepresented in AD women with p = 0.014 (Bonferroni corrected p = 0.252). A specific haplotype block consisting of SNPs rs11669576, rs2738444 and rs5925 was identified and in women the haplotype GTT was overrepresented in AD cases when compared to controls with p = 0.008. We measured CSF Aβ₄₂, tau and phosphorylated tau (ptau) levels in a subgroup of cases and controls and found that some genotypes were associated with increased levels of tau and ptau or a decreased Aβ₄₂ level in women. The specific risk haplotype GTT was associated with an increased level of tau and ptau in both men and women. Our findings suggest that LDLR gene may be associated with AD risk and its CSF biomarkers, especially in women.