Influence of SORL1 gene variants: Association with CSF amyloid-beta products in probable Alzheimer's disease

SORL1 gene variants were described as risk factors of Alzheimer's disease (AD). We investigated the association of four SORL1 variants with CSF levels of A beta(42) and A beta(40) in 153 AD patients recruited from a multicenter study of the German Competence Net Dementias. Only one SORL1 SNP was associated with altered A beta(42) levels in the single marker analysis (SNP21: p = 0.011), the other SNPs did not show an association with A beta(42) orA beta(40) CSF levels. Haplotype analysis identified a three marker SORL1 haplotype consisting of SNP19 T-allele, SNP21 G-allele and SNP23 A-allele (T/G/A) which was associated with reduced A beta(42) CSF levels in AD patients (p = 0.003). A beta(40) levels were also lower in carriers of this haplotype; however, this did not reach statistical significance (p = 0.15). We found a SORL1 haplotype which was associated with CSF levels of amyloid-P cleavage products, measured as altered levels of A beta(42). Thus our data suggest that: SORL1 gene variants might influence AD pathology. (C) 2008 Elsevier Ireland Ltd. All rights reserved.