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

[71]

Van Cauwenberghe C., 2015, Genet Med

[72] Rare coding mutations identified by sequencing of Alzheimer disease genome-wide association studies loci [J].

Vardarajan, Badri N. ;

Ghani, Mahdi ;

Kahn, Amanda ;

Sheikh, Stephanie ;

Sato, Christine ;

Barral, Sandra ;

Lee, Joseph H. ;

Cheng, Rong ;

Reitz, Christiane ;

Lantigua, Rafael ;

Reyes-Dumeyer, Dolly ;

Medrano, Martin ;

Jimenez-Velazquez, Ivonne Z. ;

Rogaeva, Ekaterina ;

St George-Hyslop, Peter ;

Mayeux, Richard .

ANNALS OF NEUROLOGY, 2015, 78 (03) :487-498

[73] TREM2 Lipid Sensing Sustains the Microglial Response in an Alzheimer's Disease Model [J].

Wang, Yaming ;

Cella, Marina ;

Mallinson, Kaitlin ;

Ulrich, Jason D. ;

Young, Katherine L. ;

Robinette, Michelle L. ;

Gilfillan, Susan ;

Krishnan, Gokul M. ;

Sudhakar, Shwetha ;

Zinselmeyer, Bernd H. ;

Holtzman, David M. ;

Cirrito, John R. ;

Colonna, Marco .

CELL, 2015, 160 (06) :1061-1071

[74] A rare mutation in UNC5C predisposes to late-onset Alzheimer's disease and increases neuronal cell death [J].

Wetzel-Smith, Monica K. ;

Hunkapiller, Julie ;

Bhangale, Tushar R. ;

Srinivasan, Karpagam ;

Maloney, Janice A. ;

Atwal, Jasvinder K. ;

Sa, Susan M. ;

Yaylaoglu, Murat B. ;

Foreman, Oded ;

Ortmann, Ward ;

Rathore, Nisha ;

Hansen, David V. ;

Tessier-Lavigne, Marc ;

Mayeux, Richard ;

Pericak-Vance, Margaret ;

Haines, Jonathan ;

Farrer, Lindsay A. ;

Schellenberg, Gerard D. ;

Goate, Alison ;

Behrens, Timothy W. ;

Cruchaga, Carlos ;

Watts, Ryan J. ;

Graham, Robert R. .

NATURE MEDICINE, 2014, 20 (12) :1452-1457

[75] Sorting receptor SORLA - a trafficking path to avoid Alzheimer disease [J].

Willnow, Thomas E. ;

Andersen, Olav M. .

JOURNAL OF CELL SCIENCE, 2013, 126 (13) :2751-2760

[76] Role of Phosphatidylinositol Clathrin Assembly Lymphoid-Myeloid Leukemia (PICALM) in Intracellular Amyloid Precursor Protein (APP) Processing and Amyloid Plaque Pathogenesis [J].

Xiao, Qingli ;

Gil, So-Chon ;

Yan, Ping ;

Wang, Yan ;

Han, Sharon ;

Gonzales, Ernie ;

Perez, Ronaldo ;

Cirrito, John R. ;

Lee, Jin-Moo .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (25) :21279-21289

← 1 2 3 4 5 6 7 8 →