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

Tools

Item Type:	Article
Title:	The influence of genetic variants in SORL1 gene on the manifestation of Alzheimer's disease
Creators Name:	Louwersheimer, E., Ramirez, A., Cruchaga, C., Becker, T., Kornhuber, J., Peters, O., Heilmann, S., Wiltfang, J., Jessen, F., Visser, P.J., Scheltens, P., Pijnenburg, Y.A.L., Teunissen, C.E., Barkhof, F., van Swieten, J.C., Holstege, H. and van der Flier, W.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.
Keywords:	Alzheimer's Disease, SORL1, Endophenotypes, SNPs
Source:	Neurobiology of Aging
ISSN:	0197-4580
Publisher:	Elsevier
Volume:	36
Number:	3
Page Range:	1605.e13-1605.e20
Date:	March 2015
Official Publication:	https://doi.org/10.1016/j.neurobiolaging.2014.12.007
PubMed:	View item in PubMed

Repository Staff Only: item control page