Molecular mechanisms of the genetic risk factors in pathogenesis of Alzheimer disease

被引：15

作者：

Kanatsu, Kunihiko ^{[1
]}

Tomita, Taisuke ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Pharmaceut Sci, Lab Neuropathol & Neurosci, Tokyo 1138654, Japan

来源：

FRONTIERS IN BIOSCIENCE-LANDMARK | 2017年 / 22卷

基金：

日本学术振兴会;

关键词：

Alzheimer disease; Genetic Risk Factor; Trafficking; Lipid; Immune System; Review; AMYLOID PRECURSOR PROTEIN; GENOME-WIDE ASSOCIATION; APOLIPOPROTEIN-E; A-BETA; GAMMA-SECRETASE; MOUSE MODEL; IDENTIFIES VARIANTS; COMMON VARIANTS; IN-VIVO; MUTATIONS;

D O I：

10.2741/4480

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Alzheimer disease (AD) is a neurodegenerative disease characterized by the extensive deposition of senile plaques and neurofibrillary tangles. Until recently, only the APOE gene had been known as a genetic risk factor for late-onset AD (LOAD), which accounts for more than 95% of all AD cases. However, in addition to this well-established genetic risk factor, genomewide association studies have identified several single nucleotide polymorphisms as genetic risk factors of LOAD, such as PICALM and BIN1. In addition, whole genome sequencing and exome sequencing have identified rare variants associated with LOAD, including TREM2. We review the recent findings related to the molecular mechanisms by which these genetic risk factors contribute to AD, and our perspectives regarding the etiology of AD for the development of therapeutic agents.

引用

页码：180 / 192

页数：13

共 76 条

[1] Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein [J].

Andersen, OM ;

Reiche, J ;

Schmidt, V ;

Gotthardt, M ;

Spoelgen, R ;

Behlke, J ;

von Arnim, CAF ;

Breiderhoff, T ;

Jansen, P ;

Wu, X ;

Bales, KR ;

Cappai, R ;

Masters, CL ;

Gliemann, J ;

Mufson, EJ ;

Hyman, BT ;

Paul, SM ;

Nykjær, A ;

Willnow, TE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (38) :13461-13466

[2] Apolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) [J].

Atagi, Yuka ;

Liu, Chia-Chen ;

Painter, Meghan M. ;

Chen, Xiao-Fen ;

Verbeeck, Christophe ;

Zheng, Honghua ;

Li, Xia ;

Rademakers, Rosa ;

Kang, Silvia S. ;

Xu, Huaxi ;

Younkin, Steven ;

Das, Pritam ;

Fryer, John D. ;

Bu, Guojun .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2015, 290 (43) :26043-26050

[3] The Triggering Receptor Expressed on Myeloid Cells 2 Binds Apolipoprotein E [J].

Bailey, Charles C. ;

DeVaux, Lindsey B. ;

Farzan, Michael .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2015, 290 (43) :26033-26042

[4] 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

[5] Missense variant in TREML2 protects against Alzheimer's disease [J].

Benitez, Bruno A. ;

Jin, Sheng Chih ;

Guerreiro, Rita ;

Graham, Rob ;

Lord, Jenny ;

Harold, Denise ;

Sims, Rebecca ;

Lambert, Jean-Charles ;

Gibbs, J. Raphael ;

Bras, Jose ;

Sassi, Celeste ;

Harari, Oscar ;

Bertelsen, Sarah ;

Lupton, Michelle K. ;

Powell, John ;

Bellenguez, Celine ;

Brown, Kristelle ;

Medway, Christopher ;

Haddick, Patrick C. G. ;

van der Brug, Marcel P. ;

Bhangale, Tushar ;

Ortmann, Ward ;

Behrens, Tim ;

Mayeux, Richard ;

Pericak-Vance, Margaret A. ;

Farrer, Lindsay A. ;

Schellenberg, Gerard D. ;

Haines, Jonathan L. ;

Turton, Jim ;

Braae, Anne ;

Barber, Imelda ;

Fagan, Anne M. ;

Holtzman, David M. ;

Morris, John C. ;

Williams, Julie ;

Kauwe, John S. K. ;

Amouyel, Philippe ;

Morgan, Kevin ;

Singleton, Andy ;

Hardy, John ;

Goate, Alison M. ;

Cruchaga, Carlos .

NEUROBIOLOGY OF AGING, 2014, 35 (06) :1510.e19-1510.e26

[6] Heterozygous TREM2 mutations in frontotemporal dementia [J].

Borroni, Barbara ;

Ferrari, Francesca ;

Galimberti, Daniela ;

Nacmias, Benedetta ;

Barone, Cinzia ;

Bagnoli, Silvia ;

Fenoglio, Chiara ;

Piaceri, Irene ;

Archetti, Silvana ;

Bonvicini, Cristian ;

Gennarelli, Massimo ;

Turla, Marinella ;

Scarpini, Elio ;

Sorbi, Sandro ;

Padovani, Alessandro .

NEUROBIOLOGY OF AGING, 2014, 35 (04) :934.e7-934.e10

[7] CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology [J].

Bradshaw, Elizabeth M. ;

Chibnik, Lori B. ;

Keenan, Brendan T. ;

Ottoboni, Linda ;

Raj, Towfique ;

Tang, Anna ;

Rosenkrantz, Laura L. ;

Imboywa, Selina ;

Lee, Michelle ;

Von Korff, Alina ;

Morris, Martha C. ;

Evans, Denis A. ;

Johnson, Keith ;

Sperling, Reisa A. ;

Schneider, Julie A. ;

Bennett, David A. ;

De Jager, Philip L. .

NATURE NEUROSCIENCE, 2013, 16 (07) :848-U92

[8] Lysosomal Sorting of Amyloid-β by the SORLA Receptor Is Impaired by a Familial Alzheimer's Disease Mutation [J].

Caglayan, Safak ;

Takagi-Niidome, Shizuka ;

Liao, Fan ;

Carlo, Anne-Sophie ;

Schmidt, Vanessa ;

Burgert, Tilman ;

Kitago, Yu ;

Fuechtbauer, Ernst-Martin ;

Fuechtbauer, Annette ;

Holtzman, David M. ;

Takagi, Junichi ;

Willnow, Thomas E. .

SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (223)

[9] CD33 modulates TREM2: convergence of Alzheimer loci [J].

Chan, Gail ;

White, Charles C. ;

Winn, Phoebe A. ;

Cimpean, Maria ;

Replogle, Joseph M. ;

Glick, Laura R. ;

Cuerdon, Nicole E. ;

Ryan, Katie J. ;

Johnson, Keith A. ;

Schneider, Julie A. ;

Bennett, David A. ;

Chibnik, Lori B. ;

Sperling, Reisa A. ;

Bradshaw, Elizabeth M. ;

De Jager, Philip L. .

NATURE NEUROSCIENCE, 2015, 18 (11) :1556-1558

[10] Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology [J].

Chapuis, J. ;

Hansmannel, F. ;

Gistelinck, M. ;

Mounier, A. ;

Van Cauwenberghe, C. ;

Kolen, K. V. ;

Geller, F. ;

Sottejeau, Y. ;

Harold, D. ;

Dourlen, P. ;

Grenier-Boley, B. ;

Kamatani, Y. ;

Delepine, B. ;

Demiautte, F. ;

Zelenika, D. ;

Zommer, N. ;

Hamdane, M. ;

Bellenguez, C. ;

Dartigues, J-F ;

Hauw, J-J ;

Letronne, F. ;

Ayral, A-M ;

Sleegers, K. ;

Schellens, A. ;

Broeck, L. V. ;

Engelborghs, S. ;

De Deyn, P. P. ;

Vandenberghe, R. ;

O'Donovan, M. ;

Owen, M. ;

Epelbaum, J. ;

Mercken, M. ;

Karran, E. ;

Bantscheff, M. ;

Drewes, G. ;

Joberty, G. ;

Campion, D. ;

Octave, J-N ;

Berr, C. ;

Lathrop, M. ;

Callaerts, P. ;

Mann, D. ;

Williams, J. ;

Buee, L. ;

Dewachter, I. ;

Van Broeckhoven, C. ;

Amouyel, P. ;

Moechars, D. ;

Dermaut, B. ;

Lambert, J-C .

MOLECULAR PSYCHIATRY, 2013, 18 (11) :1225-1234

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