The influence of genetic variants in SORL1 gene on the manifestation of Alzheimer's disease
2014 | journal article
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The 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. et al. (2014)
Neurobiology of Aging, 36(3) pp. 1605.e13-1605.e20. DOI: https://doi.org/10.1016/j.neurobiolaging.2014.12.007
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- Authors
- Louwersheimer, Eva; Ramirez, Alfredo; Cruchaga, Carlos; Becker, Tim; Kornhuber, Johannes ; Peters, Oliver; Heilmann, Stefanie; Wiltfang, Jens ; Jessen, Frank; Visser, Pieter Jelle; Scheltens, Philip; Pijnenburg, Yolande A.L.; Teunissen, Charlotte E.; Barkhof, Frederik; van Swieten, John C.; Holstege, Henne; Van der Flier, Wiesje M.
- 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.
- Issue Date
- 2014
- Journal
- Neurobiology of Aging
- ISSN
- 0197-4580
- Language
- English