Andersson, C-H;
Hansson, O;
Minthon, L;
Andreasen, N;
Blennow, K;
Zetterberg, H;
Skoog, I;
... Kettunen, P; + view all
(2016)
A Genetic Variant of the Sortilin 1 Gene is Associated with Reduced Risk of Alzheimer's Disease.
Journal of Alzheimer's Disease
, 53
(4)
pp. 1353-1363.
10.3233/JAD-160319.
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Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder represented by the accumulation of intracellular tau protein and extracellular deposits of amyloid-β (Aβ) in the brain. The gene sortilin 1 (SORT1) has previously been associated with cardiovascular disease in gene association studies. It has also been proposed to be involved in AD pathogenesis through facilitating Aβ clearance by binding apoE/Aβ complexes prior to cellular uptake. However, the neuropathological role of SORT1 in AD is not fully understood. To evaluate the associations between gene variants of SORT1 and risk of AD, we performed genetic analyses in a Swedish case-control cohort. Ten single nucleotide polymorphisms (SNPs), covering the whole SORT1 gene, were selected and genotyped in 620 AD patients and 1107 controls. The SNP rs17646665, located in a non-coding region of the SORT1 gene, remained significantly associated with decreased risk of AD after multiple testing (pc = 0.0061). In addition, other SNPs were found to be nominally associated with risk of AD, as well as altered cognitive function and the CSF biomarker Aβ42, but these associations did not survive correction for multiple testing. The fact that SORT1 has been strongly associated with risk of cardiovascular disease is intriguing as cardiovascular disease is also regarded as a risk factor for AD. Finally, increased knowledge about SORT1 function has a potential to increase our understanding of APOE, the strongest risk factor for AD.
| Type: | Article |
|---|---|
| Title: | A Genetic Variant of the Sortilin 1 Gene is Associated with Reduced Risk of Alzheimer's Disease |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3233/JAD-160319 |
| Publisher version: | http://dx.doi.org/10.3233/JAD-160319 |
| Language: | English |
| Additional information: | Copyright © 2016 – IOS Press and the authors. This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0). |
| Keywords: | Amyloid beta-peptides, apolipoprotein E, biomarkers, genetic association studies, genotype, neuropsychological tests, risk factors, single nucleotide polymorphism, tau proteins, vesicular transport adaptor proteins |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1537841 |
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