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

Louwersheimer E, Ramirez A, Cruchaga C, Becker T, Kornhuber J, Peters O, Heilmann S, Wiltfang J, Jessen F, Visser PJ, Scheltens P, Pijnenburg YAL, Teunissen CE, Barkhof F, Van Swieten JC, Holstege H, Van Der Flier WM (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Neurobiology of Aging Elsevier

Book Volume: 36

Pages Range: 1605.e13-20

Journal Issue: 3

DOI: 10.1016/j.neurobiolaging.2014.12.007

Abstract

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.

Authors with CRIS profile

Johannes Kornhuber Lehrstuhl für Psychiatrie und Psychotherapie

Involved external institutions

Vrije Universiteit Amsterdam (VU) / University Amsterdam NL Netherlands (NL) Erasmus University Medical Center (MC) NL Netherlands (NL) Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Georg-August-Universität Göttingen DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) DE Germany (DE) Washington University US United States (USA) (US)

How to cite

APA:

Louwersheimer, E., Ramirez, A., Cruchaga, C., Becker, T., Kornhuber, J., Peters, O.,... Van Der Flier, W.M. (2015). Influence of genetic variants in SORL1 gene on the manifestation of Alzheimer's disease. Neurobiology of Aging, 36(3), 1605.e13-20. https://doi.org/10.1016/j.neurobiolaging.2014.12.007

MLA:

Louwersheimer, Eva, et al. "Influence of genetic variants in SORL1 gene on the manifestation of Alzheimer's disease." Neurobiology of Aging 36.3 (2015): 1605.e13-20.

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