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A Genetic Variant of the Sortilin 1 Gene is Associated with Reduced Risk of Alzheimer's Disease

Andersson, Carl Henrik; Hansson, Oskar LU ; Minthon, Lennart LU ; Andreasen, Niels; Blennow, Kaj LU ; Zetterberg, Henrik LU ; Skoog, Ingmar; Wallin, Anders; Nilsson, Staffan and Kettunen, Petronella (2016) In Journal of Alzheimer's Disease 53(4). p.1353-1363
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Alzheimer's Disease
volume
53
issue
4
pages
11 pages
publisher
IOS Press
external identifiers
  • scopus:84981713498
  • wos:000383149600010
ISSN
1387-2877
DOI
10.3233/JAD-160319
language
English
LU publication?
yes
id
b9d5b830-67c9-4c73-a638-7e4b811eb14f
date added to LUP
2016-10-10 10:04:42
date last changed
2017-07-09 04:53:43
@article{b9d5b830-67c9-4c73-a638-7e4b811eb14f,
  abstract     = {<p>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.</p>},
  author       = {Andersson, Carl Henrik and Hansson, Oskar and Minthon, Lennart and Andreasen, Niels and Blennow, Kaj and Zetterberg, Henrik and Skoog, Ingmar and Wallin, Anders and Nilsson, Staffan and Kettunen, Petronella},
  issn         = {1387-2877},
  language     = {eng},
  number       = {4},
  pages        = {1353--1363},
  publisher    = {IOS Press},
  series       = {Journal of Alzheimer's Disease},
  title        = {A Genetic Variant of the Sortilin 1 Gene is Associated with Reduced Risk of Alzheimer's Disease},
  url          = {http://dx.doi.org/10.3233/JAD-160319},
  volume       = {53},
  year         = {2016},
}