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

Authors

Heike Kolsch, University of Bonn
Frank Jessen, University of Bonn
Jens Wiltfang, University of Erlangen-Nuremberg
Piotr Lewczuk, University of Erlangen-Nuremberg
Martin Dichgans, University of Munich
Johannes Kornhuber, Friedrich-Alexander-University of Erlangen-Nuremberg
Lutz Frolich, Central Institute of Mental Health
Isabella Heuser, Charite-University of Medicine
Oliver Peters, Charite-University of Medicine
Jorg B. Schulz, University of Gottingen
Sibylle G. Schwab, University of Western AustraliaFollow
Wolfgang Maier, University of Bonn

RIS ID

95817

Publication Details

Kolsch, H., Jessen, F., Wiltfang, J., Lewczuk, P., Dichgans, M., Kornhuber, J., Frolich, L., Heuser, I., Peters, O., Schulz, J. B., Schwab, S. G. & Maier, W. (2008). Influence of SORL1 gene variants: association with CSF amyloid-β products in probable Alzheimer's disease. Neuroscience Letters, 440 (1), 68-71.

Abstract

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 Aβ42 and Aβ40 in 153 AD patients recruited from a multicenter study of the German Competence Net Dementias. Only one SORL1 SNP was associated with altered Aβ42 levels in the single marker analysis (SNP21: p = 0.011), the other SNPs did not show an association with Aβ42 or Aβ40 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 Aβ42 CSF levels in AD patients (p = 0.003). Aβ40 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-β cleavage products, measured as altered levels of Aβ42. Thus our data suggest that SORL1 gene variants might influence AD pathology.