The influence of genetic variants in SORL1 gene on the manifestation of Alzheimer's disease

Eva Louwersheimer*, Alfredo Ramirez, Carlos Cruchaga, Tim Becker, Johannes Kornhuber, Oliver Peters, Stefanie Heilmann, Jens Wiltfang, Frank Jessen, Pieter Jelle Visser, Philip Scheltens, Yolande A. L. Pijnenburg, Charlotte E. Teunissen, Frederik Barkhof, John C. van Swieten, Henne Holstege, Wiesje M. Van der Flier

*Corresponding author for this work

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We studied the association of SORL1 single-nucleotide polymorphisms genotypes with measures of pathology in patients with probable Alzheimer's disease (AD) using an endophenotype approach. We included (1) 133 patients from the German Dementia Competence Network (71 +/- 8 years; 50% females; Mini Mental State Examination [MMSE], 24 +/- 3); (2) 83 patients from the Alzheimer's Disease Neuroimaging Initiative (75 +/- 8 years; 45% females; MMSE, 24 +/- 2); and (3) 452 patients from the Amsterdam Dementia Cohort 66 +/- 8 years; 47% females; MMSE, 20 +/- 5). As endophenotype markers we used cognitive tests, cerebrospinal fluid (CSF) biomarkers amyloid-beta, total tau (tau), tau phosphorylated at threonine 181, and hippocampal atrophy. We measured 19 SORL1 SNP alleles. Genotype-endophenotype associations were determined by linear regression analyses. There was an association between rs2070045-G allele and increased CSF-tau and more hippocampal atrophy. Additionally, haplotype-based analyses revealed an association between haplotype rs11218340-A/rs3824966-G/rs3824968-A and higher CSF-tau and CSF-tau phosphorylated at threonine 181. In conclusion, we found that SORL1 SNP rs2070045-G allele was related to CSF-tau and hippocampal atrophy, 2 endophenotype markers of AD, suggesting that SORL1 may be implicated in the downstream pathology in AD.
Original languageEnglish
Pages (from-to)1605.e13–1605.e20
JournalNeurobiology of Aging
Issue number3
Publication statusPublished - Mar 2015


  • Alzheimer's disease
  • SORL1
  • Endophenotypes
  • SNPs

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