Journal
NEUROBIOLOGY OF AGING
Volume 36, Issue 3, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2014.12.007
Keywords
Alzheimer's disease; SORL1; Endophenotypes; SNPs
Categories
Funding
- German Federal Ministry for Education and Research [01GI0422]
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health grant) [U01 AG024904]
- DOD ADNI (Department of Defense award) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- BioClinica
- Biogen Idec Inc
- Bristol-Myers Squibb Company
- Eisai Inc
- Elan Pharmaceuticals, Inc
- Eli Lilly and Company
- F. Hoffmann-La Roche Ltd
- Genentech
- GE Healthcare
- Innogenetics
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC
- Johnson & Johnson Pharmaceutical Research& Development LLC
- Medpace, Inc
- Merck Co, Inc
- Meso Scale Diagnostics, LLC
- NeuroRx Research
- Novartis Pharmaceuticals Corporation
- Pfizer Inc
- Piramal Imaging
- Servier
- Synarc Inc
- Takeda Pharmaceutical Company
- Canadian Institutes of Health Research
- Alzheimer Nederland
- Stichting VUmc fonds
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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. (C) 2015 Elsevier Inc. All rights reserved.
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