Cyclin-dependent kinase 5 is associated with risk for Alzheimer's disease in a Dutch population-based study

Although the role of the Cdk5 protein in Alzheimer's disease (AD) is well recognized, there have been relatively few studies investigating genetic variants in the CDK5 gene in AD. In this study, we assessed the association between five previously described single nucleotide polymorphisms (SNPs) in the CDK5 gene and late onset AD by means of logistic regression and haplotype association analyses. Including all prevalent and incident AD cases, we found a significantly increased risk of AD for carriers of the GG genotype of SNP rs2069442 (OR = 1.79, 95 % CI 1.16-2.79, p = 0.001) in those without APOE*4. When limiting the analysis to incident cases without APOE*4, carriers of the GG genotype showed a 1.9-fold increased risk of AD (95 % CI 1.16-3.10, p = 0.003). Variations in the CDK5 gene can be described in 5 haplotype blocks. In our analysis, the haplotype tagged by the G allele of SNP rs2069442 was significantly associated with AD (p = 0.05). In conclusion, our study suggests that CDK5 may be associated with AD.