Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy

被引:846
作者
Bu, Guojun [1 ,2 ]
机构
[1] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, Dept Pediat, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA
关键词
DENSITY-LIPOPROTEIN RECEPTOR; AMYLOID PRECURSOR PROTEIN; CENTRAL-NERVOUS-SYSTEM; BETA-PEPTIDE DEPOSITION; KNOCK-IN MICE; A-BETA; TRANSGENIC MICE; CELL-SURFACE; APOE ISOFORM; MOUSE MODEL;
D O I
10.1038/nrn2620
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 and their development is probably influenced by both genetic and environmental risk factors. A strong genetic risk factor for late-onset AD is the presence of the epsilon 4 allele of the apolipoprotein E (APOE) gene, which encodes a protein with crucial roles in cholesterol metabolism. There is mounting evidence that APOE4 contributes to AD pathogenesis by modulating the metabolism and aggregation of amyloid-beta peptide and by directly regulating brain lipid metabolism and synaptic functions through APOE receptors. Emerging knowledge of the contribution of APOE to the pathophysiology of AD presents new opportunities for AD therapy.
引用
收藏
页码:333 / 344
页数:12
相关论文
共 153 条
[31]   Apolipoprotein E-containing high density lipoprotein promotes neurite outgrowth and is a ligand for the low density lipoprotein receptor-related protein [J].
Fagan, AM ;
Bu, GJ ;
Sun, YL ;
Daugherty, A ;
Holtzman, DM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (47) :30121-30125
[32]   The low density lipoprotein receptor regulates the level of central nervous system human and murine apolipoprotein E but does not modify amyloid plaque pathology in PDAPP mice [J].
Fryer, JD ;
DeMattos, RB ;
McCormick, LM ;
O'Dell, MA ;
Spinner, ML ;
Bales, KR ;
Paul, SM ;
Sullivan, PM ;
Parsadanian, M ;
Bu, GJ ;
Holtzman, DM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (27) :25754-25759
[33]   Human apolipoprotein E4 alters the amyloid-β 40:42 ratio and promotes the formation of cerebral amyloid angiopathy in an amyloid precursor protein transgenic model [J].
Fryer, JD ;
Simmons, K ;
Parsadanian, M ;
Bales, KR ;
Paul, SM ;
Sullivan, PM ;
Holtzman, DM .
JOURNAL OF NEUROSCIENCE, 2005, 25 (11) :2803-2810
[34]   RECEPTOR-MEDIATED ENDOCYTOSIS - CONCEPTS EMERGING FROM THE LDL RECEPTOR SYSTEM [J].
GOLDSTEIN, JL ;
BROWN, MS ;
ANDERSON, RGW ;
RUSSELL, DW ;
SCHNEIDER, WJ .
ANNUAL REVIEW OF CELL BIOLOGY, 1985, 1 :1-39
[35]   Apolipoprotein E (ApoE) isoform-dependent lipid release from astrocytes prepared from human ApoE3 and ApoE4 knock-in mice [J].
Gong, JS ;
Kobayashi, M ;
Hayashi, H ;
Zou, K ;
Sawamura, N ;
Fujita, SC ;
Yanagisawa, K ;
Michikawa, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (33) :29919-29926
[36]   APOLIPOPROTEIN-E EPSILON-4 AND CEREBRAL-HEMORRHAGE ASSOCIATED WITH AMYLOID ANGIOPATHY [J].
GREENBERG, SM ;
REBECK, GW ;
VONSATTEL, JPG ;
GOMEZISLA, T ;
HYMAN, BT .
ANNALS OF NEUROLOGY, 1995, 38 (02) :254-259
[37]   Soluble low-density lipoprotein receptor-related protein [J].
Grimsley, PG ;
Quinn, KA ;
Owensby, DA .
TRENDS IN CARDIOVASCULAR MEDICINE, 1998, 8 (08) :363-368
[38]   Altered cholesterol metabolism in human apolipoprotein E4 knock-in mice [J].
Hamanaka, H ;
Katoh-Fukui, Y ;
Suzuki, K ;
Kobayashi, M ;
Suzuki, R ;
Motegi, Y ;
Nakahara, Y ;
Takeshita, A ;
Kawai, M ;
Ishiguro, K ;
Yokoyama, M ;
Fujita, SC .
HUMAN MOLECULAR GENETICS, 2000, 9 (03) :353-361
[39]   Potential mechanisms contributing to sulfatide depletion at the earliest clinically recognizable stage of Alzheimer's disease: a tale of shotgun lipidomics [J].
Han, Xianlin .
JOURNAL OF NEUROCHEMISTRY, 2007, 103 :171-179
[40]   Medicine - The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics [J].
Hardy, J ;
Selkoe, DJ .
SCIENCE, 2002, 297 (5580) :353-356