Apolipoprotein E in Alzheimer's Disease: An Update

被引:310
作者
Yu, Jin-Tai [1 ,2 ]
Tan, Lan [1 ,2 ]
Hardy, John [3 ,4 ]
机构
[1] Qingdao Univ, Sch Med, Qingdao Municipal Hosp, Dept Neurol, Qingdao 266071, Peoples R China
[2] Ocean Univ China, Coll Med & Pharmaceut, Qingdao 266003, Peoples R China
[3] UCL, Inst Neurol, Reta Lila Weston Labs, London WC1N 3BG, England
[4] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England
来源
ANNUAL REVIEW OF NEUROSCIENCE, VOL 37 | 2014年 / 37卷
基金
中国国家自然科学基金;
关键词
Alzheimer's disease; apolipoprotein E; polymorphism; amyloid-beta; tau; pathogenesis; therapy; TRANSGENIC MOUSE MODEL; BETA A-BETA; REDUCES AMYLOID DEPOSITION; APOE GENOTYPE; GENETIC RISK; DEPENDENT IMPAIRMENT; BEHAVIORAL DEFICITS; GLUCOSE-METABOLISM; EPSILON-4; ALLELE; IN-VITRO;
D O I
10.1146/annurev-neuro-071013-014300
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The vast majority of Alzheimer's disease (AD) cases are late onset (LOAD), which is genetically complex with heritability estimates up to 80%. Apolipoprotein E (APOE) has been irrefutably recognized as the major genetic risk factor, with semidominant inheritance, for LOAD. Although the mechanisms that underlie the pathogenic nature of APOE in AD are still not completely understood, emerging data suggest that APOE contributes to AD pathogenesis through both amyloid-beta (A beta)-dependent and A beta-independent pathways. Given the central role for APOE in the modulation of AD pathogenesis, many therapeutic strategies have emerged, including converting APOE conformation, regulating APOE expression, mimicking APOE peptides, blocking the APOE/A beta interaction, modulating APOE lipidation state, and gene therapy. Accumulating evidence also suggests the utility of APOE genotyping in AD diagnosis, risk assessment, prevention, and treatment response.
引用
收藏
页码:79 / 100
页数:22
相关论文
共 145 条
[71]   Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis [J].
Kim, Jungsu ;
Eltorai, Adam E. M. ;
Jiang, Hong ;
Liao, Fan ;
Verghese, Philip B. ;
Kim, Jaekwang ;
Stewart, Floy R. ;
Basak, Jacob M. ;
Holtzman, David M. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2012, 209 (12) :2149-2156
[72]   Haploinsufficiency of Human APOE Reduces Amyloid Deposition in a Mouse Model of Amyloid-β Amyloidosis [J].
Kim, Jungsu ;
Jiang, Hong ;
Park, Seonha ;
Eltorai, Adam E. M. ;
Stewart, Floy R. ;
Yoon, Hyejin ;
Basak, Jacob M. ;
Finn, Mary Beth ;
Holtzman, David M. .
JOURNAL OF NEUROSCIENCE, 2011, 31 (49) :18007-18012
[73]   The Role of Apolipoprotein E in Alzheimer's Disease [J].
Kim, Jungsu ;
Basak, Jacob M. ;
Holtzman, David M. .
NEURON, 2009, 63 (03) :287-303
[74]   PROGRESSIVE LOSS OF SYNAPTIC INTEGRITY IN HUMAN APOLIPOPROTEIN E4 TARGETED REPLACEMENT MICE AND ATTENUATION BY APOLIPOPROTEIN E2 [J].
Klein, R. C. ;
Mace, B. E. ;
Moore, S. D. ;
Sullivan, P. M. .
NEUROSCIENCE, 2010, 171 (04) :1265-1272
[75]   Apolipoprotein E4 effects in Alzheimer's disease are mediated by synaptotoxic oligomeric amyloid-β [J].
Koffie, Robert M. ;
Hashimoto, Tadafumi ;
Tai, Hwan-Ching ;
Kay, Kevin R. ;
Serrano-Pozo, Alberto ;
Joyner, Daniel ;
Hou, Steven ;
Kopeikina, Katherine J. ;
Frosch, Matthew P. ;
Lee, Virginia M. ;
Holtzman, David M. ;
Hyman, Bradley T. ;
Spires-Jones, Tara L. .
BRAIN, 2012, 135 :2155-2168
[76]   ApoE isoform-dependent changes in hippocampal synaptic function [J].
Korwek, Kimberly M. ;
Trotter, Justin H. ;
LaDu, Mary Jo ;
Sullivan, Patrick M. ;
Weeber, Edwin J. .
MOLECULAR NEURODEGENERATION, 2009, 4
[77]   Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration [J].
Kuszczyk, Magdalena A. ;
Sanchez, Sandrine ;
Pankiewicz, Joanna ;
Kim, Jungsu ;
Duszczyk, Malgorzata ;
Guridi, Maitea ;
Asuni, Ayodeji A. ;
Sullivan, Patrick M. ;
Holtzman, David M. ;
Sadowski, Martin J. .
AMERICAN JOURNAL OF PATHOLOGY, 2013, 182 (05) :1750-1768
[78]   Distortion of allelic expression of apolipoprotein E in Alzheimer's disease [J].
Lambert, JC ;
PerezTur, J ;
Dupire, MJ ;
Galasko, D ;
Mann, D ;
Amouyel, P ;
Hardy, J ;
Delacourte, A ;
ChartierHarlin, MC .
HUMAN MOLECULAR GENETICS, 1997, 6 (12) :2151-2154
[79]   Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease [J].
Lambert, Jean-Charles ;
Ibrahim-Verbaas, Carla A. ;
Harold, Denise ;
Naj, Adam C. ;
Sims, Rebecca ;
Bellenguez, Celine ;
Jun, Gyungah ;
DeStefano, Anita L. ;
Bis, Joshua C. ;
Beecham, Gary W. ;
Grenier-Boley, Benjamin ;
Russo, Giancarlo ;
Thornton-Wells, Tricia A. ;
Jones, Nicola ;
Smith, Albert V. ;
Chouraki, Vincent ;
Thomas, Charlene ;
Ikram, M. Arfan ;
Zelenika, Diana ;
Vardarajan, Badri N. ;
Kamatani, Yoichiro ;
Lin, Chiao-Feng ;
Gerrish, Amy ;
Schmidt, Helena ;
Kunkle, Brian ;
Dunstan, Melanie L. ;
Ruiz, Agustin ;
Bihoreau, Marie-Therese ;
Choi, Seung-Hoan ;
Reitz, Christiane ;
Pasquier, Florence ;
Hollingworth, Paul ;
Ramirez, Alfredo ;
Hanon, Olivier ;
Fitzpatrick, Annette L. ;
Buxbaum, Joseph D. ;
Campion, Dominique ;
Crane, Paul K. ;
Baldwin, Clinton ;
Becker, Tim ;
Gudnason, Vilmundur ;
Cruchaga, Carlos ;
Craig, David ;
Amin, Najaf ;
Berr, Claudine ;
Lopez, Oscar L. ;
De Jager, Philip L. ;
Deramecourt, Vincent ;
Johnston, Janet A. ;
Evans, Denis .
NATURE GENETICS, 2013, 45 (12) :1452-U206
[80]   Response to Comments on "ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models" [J].
Landreth, Gary E. ;
Cramer, Paige E. ;
Lakner, Mitchell M. ;
Cirrito, John R. ;
Wesson, Daniel W. ;
Brunden, Kurt R. ;
Wilson, Donald A. .
SCIENCE, 2013, 340 (6135)