Alzheimer's Disease Risk Genes and Mechanisms of Disease Pathogenesis

被引：946

作者：

Karch, Celeste M.

Goate, Alison M. ^{[1
]}

机构：

[1] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

来源：

BIOLOGICAL PSYCHIATRY | 2015年 / 77卷 / 01期

关键词：

Alzheimer's Disease; Amyloid Precursor Protein; Cholesterol Metabolism; Endocytosis; Genome-Wide Association Studies; Immune Response; AMYLOID PRECURSOR PROTEIN; GENOME-WIDE ASSOCIATION; CLASSICAL COMPLEMENT PATHWAY; CASSETTE TRANSPORTER A7; FLUID TAU LEVELS; APOLIPOPROTEIN-E; MOUSE MODEL; BETA-PEPTIDE; PLASMA CLUSTERIN; FRONTOTEMPORAL DEMENTIA;

D O I：

10.1016/j.biopsych.2014.05.006

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：43 / 51

页数：9

共 151 条

[1] Novel late-onset Alzheimer disease loci variants associate with brain gene expression [J].

Allen, Mariet ;

Zou, Fanggeng ;

Chai, High Seng ;

Younkin, Curtis S. ;

Crook, Julia ;

Pankratz, V. Shane ;

Carrasquillo, Minerva M. ;

Rowley, Christopher N. ;

Nair, Asha A. ;

Middha, Sumit ;

Maharjan, Sooraj ;

Thuy Nguyen ;

Ma, Li ;

Malphrus, Kimberly G. ;

Palusak, Ryan ;

Lincoln, Sarah ;

Bisceglio, Gina ;

Georgescu, Constantin ;

Schultz, Debra ;

Rakhshan, Fariborz ;

Kolbert, Christopher P. ;

Jen, Jin ;

Haines, Jonathan L. ;

Mayeux, Richard ;

Pericak-Vance, Margaret A. ;

Farrer, Lindsay A. ;

Schellenberg, Gerard D. ;

Petersen, Ronald C. ;

Graff-Radford, Neill R. ;

Dickson, Dennis W. ;

Younkin, Steven G. ;

Ertekin-Taner, Niluefer .

NEUROLOGY, 2012, 79 (03) :221-228

[2] Distribution and Expression of Picalm in Alzheimer Disease [J].

Baig, Shabnam ;

Joseph, Sally A. ;

Tayler, Hannah ;

Abraham, Richard ;

Owen, Michael J. ;

Williams, Julie ;

Kehoe, Patrick G. ;

Love, Seth .

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2010, 69 (10) :1071-1077

[3] Lack of apolipoprotein E dramatically reduces amyloid beta-peptide deposition [J].

Bales, KR ;

Verina, T ;

Dodel, RC ;

Du, YS ;

Altstiel, L ;

Bender, M ;

Hyslop, P ;

Johnstone, EM ;

Little, SP ;

Cummins, DJ ;

Piccardo, P ;

Ghetti, B ;

Paul, SM .

NATURE GENETICS, 1997, 17 (03) :263-264

[4] TREM2 and Neurodegenerative Disease REPLY [J].

Jonsson, Thorlakur ;

Stefansson, Kari .

NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (16) :1568-1569

[5] The PSEN1, p.E318G Variant Increases the Risk of Alzheimer's Disease in APOE-ε4 Carriers [J].

Benitez, Bruno A. ;

Karch, Celeste M. ;

Cai, Yefei ;

Jin, Sheng Chih ;

Cooper, Breanna ;

Carrell, David ;

Bertelsen, Sarah ;

Chibnik, Lori ;

Schneider, Julie A. ;

Bennett, David A. ;

Fagan, Anne M. ;

Holtzman, David ;

Morris, John C. ;

Goate, Alison M. ;

Cruchaga, Carlos .

PLOS GENETICS, 2013, 9 (08)

[6] Genome-wide Association Analysis Reveals Putative Alzheimer's Disease Susceptibility Loci in Addition to APOE [J].

Bertram, Lars ;

Lange, Christoph ;

Mullin, Kristina ;

Parkinson, Michele ;

Hsiao, Monica ;

Hogan, Meghan F. ;

Schjeide, Brit M. M. ;

Hooli, Basavaraj ;

DiVito, Jason ;

Ionita, Luliana ;

Jiang, Hongyu ;

Laird, Nan ;

Moscarillo, Thomas ;

Ohlsen, Kari L. ;

Elliott, Kathryn ;

Wang, Xin ;

Hu-Lince, Diane ;

Ryder, Marie ;

Murphy, Amy ;

Wagner, Steven L. ;

Blacker, Deborah ;

Becker, K. David ;

Tanzi, Rudolph E. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2008, 83 (05) :623-632

[7] TREM2 and Neurodegenerative Disease REPLY [J].

Jonsson, Thorlakur ;

Stefansson, Kari .

NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (16) :1568-1569

[8] Genetic Variation and Neuroimaging Measures in Alzheimer Disease [J].

Biffi, Alessandro ;

Anderson, Christopher D. ;

Desikan, Rahul S. ;

Sabuncu, Mert ;

Cortellini, Lynelle ;

Schmansky, Nick ;

Salat, David ;

Rosand, Jonathan .

ARCHIVES OF NEUROLOGY, 2010, 67 (06) :677-685

[9] TREM2 Variant p.R47H as a Risk Factor for Sporadic Amyotrophic Lateral Sclerosis [J].

Cady, Janet ;

Koval, Erica D. ;

Benitez, Bruno A. ;

Zaidman, Craig ;

Jockel-Balsarotti, Jennifer ;

Allred, Peggy ;

Baloh, Robert H. ;

Ravits, John ;

Simpson, Ericka ;

Appel, Stanley H. ;

Pestronk, Alan ;

Goate, Alison M. ;

Miller, Timothy M. ;

Cruchaga, Carlos ;

Harms, Matthew B. .

JAMA NEUROLOGY, 2014, 71 (04) :449-453

[10] Presenilin-1 uses phospholipase D1 as a negative regulator of β-amyloid formation [J].

Cai, DM ;

Netzer, WJ ;

Zhong, MH ;

Lin, YX ;

Du, GW ;

Frohman, M ;

Foster, DA ;

Sisodia, SS ;

Xu, HX ;

Gorelick, FS ;

Greengard, P .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (06) :1941-1946

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