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J Alzheimers Dis. 2016 Jul 1;53(4):1353-63. doi: 10.3233/JAD-160319.

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

Author information

1
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
2
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Sweden.
3
Memory Clinic, Skåne University Hospital, Malmö, Sweden.
4
Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden.
5
UCL Institute of Neurology, Queen Square, London, United Kingdom.
6
Department of Mathematical Sciences, Chalmers University of Technology and University of Gothenburg, Sweden.
7
Department of Neuropathology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.

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.

KEYWORDS:

Amyloid beta-peptides; apolipoprotein E; biomarkers; genetic association studies; genotype; neuropsychological tests; risk factors; single nucleotide polymorphism; tau proteins; vesicular transport adaptor proteins

PMID:
27392867
PMCID:
PMC5147507
DOI:
10.3233/JAD-160319
[Indexed for MEDLINE]
Free PMC Article

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