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PMID: 24951455 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Alzheimer's disease risk genes and mechanisms of disease pathogenesis.

Biological psychiatry ·Vol. 77 ·No. 1 ·2015-01-01 ·Pages 43-51

Karch CM, Goate AM

Abstract

We review the genetic risk factors for late-onset Alzheimer's disease (AD) and their role in AD pathogenesis. More recent advances in understanding of the human genome-technologic advances in methods to analyze millions of polymorphisms in thousands of subjects-have revealed new genes associated with AD risk, including ABCA7, BIN1, CASS4, CD33, CD2AP, CELF1, CLU, CR1, DSG2, EPHA1, FERMT2, HLA-DRB5-DBR1, INPP5D, MS4A, MEF2C, NME8, PICALM, PTK2B, SLC24H4-RIN3, SORL1, and ZCWPW1. Emerging technologies to analyze the entire genome in large data sets have also revealed coding variants that increase AD risk: PLD3 and TREM2. We review the relationship between these AD risk genes and the cellular and neuropathologic features of AD. Understanding the mechanisms underlying the association of these genes with risk for disease will provide the most meaningful targets for therapeutic development to date.

Keywords
Alzheimer’s Disease Amyloid Precursor Protein Cholesterol Metabolism Endocytosis Genome-Wide Association Studies Immune Response
MeSH Terms
Alzheimer Disease/genetics,immunology,metabolism Amyloid beta-Protein Precursor/genetics Cholesterol/metabolism Endocytosis Genetic Predisposition to Disease Genome-Wide Association Study Humans Phenotype Presenilin-1/genetics Presenilin-2/genetics Risk Factors
Chemicals
Amyloid beta-Protein Precursor PSEN1 protein, human PSEN2 protein, human Presenilin-1 Presenilin-2 Cholesterol
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Karch Celeste M
Department of Psychiatry and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri.
Goate Alison M
Department of Psychiatry and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri. Electronic address: [email protected].
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Article Info
Journal
Biological psychiatry
Abbr.
Biol Psychiatry
ISSN
1873-2402
DOI
10.1016/j.biopsych.2014.05.006
Email
[email protected]
Published
2015-01-01
Epub
2014-00-17
Pages
43-51
Language
English
Region
United States
NLM ID
0213264
PMCID
PMC4234692
Subset
IM
Grants
Wellcome Trust · 503147 · United Kingdom
NIA NIH HHS · U01 AG032438 · United States
NIA NIH HHS · P50 AG005681 · United States
Wellcome Trust · G0801418 · United Kingdom
Medical Research Council · G0801418 · United Kingdom
NIA NIH HHS · R01 AG035083 · United States
Medical Research Council · G0800509 · United Kingdom
NIA NIH HHS · K01 AG046374 · United States
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PubMed source DOI: 10.1016/j.biopsych.2014.05.006 PMC Full Text View journal details
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