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

Alzheimer's Disease Neuroimaging Initiative and Dementia Competence Network

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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 ± 8years; 50% females; Mini Mental State Examination [MMSE], 24 ± 3); (2) 83 patients from the Alzheimer's Disease Neuroimaging Initiative (75 ± 8years; 45% females; MMSE, 24 ± 2); and (3) 452 patients from the Amsterdam Dementia Cohort 66 ± 8years; 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.

Original languageEnglish
Pages (from-to)1605.e13-1605.e20
JournalNeurobiology of Aging
Volume36
Issue number3
DOIs
StatePublished - Mar 1 2015

Keywords

  • Alzheimer's disease
  • Endophenotypes
  • SNPs
  • SORL1

Fingerprint

Dive into the research topics of 'The influence of genetic variants in SORL1 gene on the manifestation of Alzheimer's disease'. Together they form a unique fingerprint.

Cite this