Association of SORL1 gene variants with Alzheimer's disease

SORL1 gene variants were described as risk factor of Alzheimer's disease (AD) additionally SORL1 gene variants were associated with altered A beta(42) CSF levels in AD patients. In the present study we investigated the association of SORL1 gene variants (rs2070045 (SNP19), SORL1-18ex26 (SNP21), rs3824968 (SNP23), rs1010159 (SNP25)) with AD risk by using Cox proportional hazard model and Kaplan-Meier survival analysis in 349 AD patients and 483 controls, recruited from a multicenter study of the German Competence Network Dementias. The SNP21G-allele and a SORL1 haplotype consisting of the SNP19 T-allele, SNP21 G-allele and SNP23 A-allele (T/G/A) were associated with increased hazard ratios and an earlier age at onset of AD (SNP21: p = 0.002; T/G/A haplotype: p = 0.007). This effect was most pronounced in carriers of an additional APOE4 allele (SNP21: p = 0.003; T/G/A haplotype: p = 0.005). In conclusion, we found SORL1 gene variants located in the 3' region of the gene to be associated with increased AD risk and an earlier age at onset of AD in our Central-European population. Thus, our data support a role of SORL1 polymorphisms in AD. (C) 2009 Elsevier B.V. All rights reserved.