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Genes associated with Alzheimer's disease: an overview and current status

Authors Giri M, Zhang M, Lü Y

Received 4 February 2016

Accepted for publication 19 March 2016

Published 17 May 2016 Volume 2016:11 Pages 665—681

DOI https://doi.org/10.2147/CIA.S105769

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lucy Goodman

Peer reviewer comments 3

Editor who approved publication: Professor Zhi-Ying Wu

Video abstract presented by Mohan Giri.

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Mohan Giri, Man Zhang, Yang Lü

Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, People’s Republic of China

Abstract: Alzheimer’s disease (AD) is a progressive, neurodegenerative disease and the most common form of dementia in elderly people. It is an emerging public health problem that poses a huge societal burden. Linkage analysis was the first milestone in unraveling the mutations in APP, PSEN1, and PSEN2 that cause early-onset AD, followed by the discovery of apolipoprotein E-ε4 allele as the only one genetic risk factor for late-onset AD. Genome-wide association studies have revolutionized genetic research and have identified over 20 genetic loci associated with late-onset AD. Recently, next-generation sequencing technologies have enabled the identification of rare disease variants, including unmasking small mutations with intermediate risk of AD in PLD3, TREM2, UNC5C, AKAP9, and ADAM10. This review provides an overview of the genetic basis of AD and the relationship between these risk genes and the neuropathologic features of AD. An understanding of genetic mechanisms underlying AD pathogenesis and the potentially implicated pathways will lead to the development of novel treatment for this devastating disease.

Keywords: Alzheimer’s disease, amyloid precursor protein, genome-wide association studies, biological pathways, presenilin 1, presenilin 2, neuropathology

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