TY - JOUR
T1 - The influence of genetic variants in SORL1 gene on the manifestation of Alzheimer's disease
AU - Louwersheimer, Eva
AU - Ramirez, Alfredo
AU - Cruchaga, Carlos
AU - Becker, Tim
AU - Kornhuber, Johannes
AU - Peters, Oliver
AU - Heilmann, Stefanie
AU - Wiltfang, Jens
AU - Jessen, Frank
AU - Visser, Pieter Jelle
AU - Scheltens, Philip
AU - Pijnenburg, Yolande A. L.
AU - Teunissen, Charlotte E.
AU - Barkhof, Frederik
AU - van Swieten, John C.
AU - Holstege, Henne
AU - Van der Flier, Wiesje M.
PY - 2015/3
Y1 - 2015/3
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - SORL1
KW - Endophenotypes
KW - SNPs
U2 - 10.1016/j.neurobiolaging.2014.12.007
DO - 10.1016/j.neurobiolaging.2014.12.007
M3 - Article
C2 - 25659857
SN - 0197-4580
VL - 36
SP - 1605.e13–1605.e20
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 3
ER -