Strategies for disease modification in Alzheimer's disease

被引:378
作者
Citron, M [1 ]
机构
[1] Amgen Inc, Dept Neurosci, Thousand Oaks, CA 91320 USA
关键词
D O I
10.1038/nrn1495
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
Treating Alzheimer's disease (AD) is the biggest unmet medical need in neurology. Current drugs improve symptoms, but do not have profound disease-modifying effects. Three main classes of disease-modification approaches can be defined: one that is broadly neurotrophic or neuroprotective, one that targets specific aspects of AD pathology, and one that is based on epidemiological observation. This review discusses all three approaches, with particular emphasis on anti-amyloid strategies-currently the most active area of investigation. The approaches that are reviewed include secretase inhibition, amyloid-beta aggregation inhibition, immunotherapy and strategies that might indirectly affect the amyloid pathway.
引用
收藏
页码:677 / 685
页数:9
相关论文
共 96 条
[1]
How do statins control neuroinflammation? [J].
Adamson, P ;
Greenwood, J .
INFLAMMATION RESEARCH, 2003, 52 (10) :399-403
[2]
Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression - A randomized controlled trial [J].
Aisen, PS ;
Schafer, KA ;
Grundman, M ;
Pfeiffer, E ;
Sano, M ;
Davis, KL ;
Farlow, MR ;
Jin, S ;
Thomas, RG ;
Thal, LJ .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2003, 289 (21) :2819-2826
[3]
NEUROFIBRILLARY TANGLES BUT NOT SENILE PLAQUES PARALLEL DURATION AND SEVERITY OF ALZHEIMERS-DISEASE [J].
ARRIAGADA, PV ;
GROWDON, JH ;
HEDLEYWHYTE, ET ;
HYMAN, BT .
NEUROLOGY, 1992, 42 (03) :631-639
[4]
Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease [J].
Bard, F ;
Cannon, C ;
Barbour, R ;
Burke, RL ;
Games, D ;
Grajeda, H ;
Guido, T ;
Hu, K ;
Huang, JP ;
Johnson-Wood, K ;
Khan, K ;
Kholodenko, D ;
Lee, M ;
Lieberburg, I ;
Motter, R ;
Nguyen, M ;
Soriano, F ;
Vasquez, N ;
Weiss, K ;
Welch, B ;
Seubert, P ;
Schenk, D ;
Yednock, T .
NATURE MEDICINE, 2000, 6 (08) :916-919
[5]
Epitope and isotype specificities of antibodies to β-amyloid peptide for protection against Alzheimer's disease-like neuropathology [J].
Bard, F ;
Barbour, R ;
Cannon, C ;
Carretto, R ;
Fox, M ;
Games, D ;
Guido, T ;
Hoenow, K ;
Hu, K ;
Johnson-Wood, K ;
Khan, K ;
Kholodenko, D ;
Lee, C ;
Lee, M ;
Motter, R ;
Nguyen, M ;
Reed, A ;
Schenk, D ;
Tang, P ;
Vasquez, N ;
Seubert, P ;
Yednock, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (04) :2023-2028
[6]
BACE1 is the major β-secretase for generation of Aβ peptides by neurons [J].
Cai, HB ;
Wang, YS ;
McCarthy, D ;
Wen, HJ ;
Borchelt, DR ;
Price, DL ;
Wong, PC .
NATURE NEUROSCIENCE, 2001, 4 (03) :233-234
[7]
PROTEIN-PHOSPHORYLATION REGULATES SECRETION OF ALZHEIMER-BETA-A4 AMYLOID PRECURSOR PROTEIN [J].
CAPORASO, GL ;
GANDY, SE ;
BUXBAUM, JD ;
RAMABHADRAN, TV ;
GREENGARD, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (07) :3055-3059
[8]
Treatment with a copper-zinc chelator markedly and rapidly inhibits β-amyloid accumulation in Alzheimer's disease transgenic mice [J].
Cherny, RA ;
Atwood, CS ;
Xilinas, ME ;
Gray, DN ;
Jones, WD ;
McLean, CA ;
Barnham, KJ ;
Volitakis, I ;
Fraser, FW ;
Kim, YS ;
Huang, XD ;
Goldstein, LE ;
Moir, RD ;
Lim, JT ;
Beyreuther, K ;
Zheng, H ;
Tanzi, RE ;
Masters, CL ;
Bush, AI .
NEURON, 2001, 30 (03) :665-676
[9]
β-Secretase inhibition for the treatment of Alzheimer's disease -: promise and challenge [J].
Citron, M .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2004, 25 (02) :92-97
[10]
GENE DOSE OF APOLIPOPROTEIN-E TYPE-4 ALLELE AND THE RISK OF ALZHEIMERS-DISEASE IN LATE-ONSET FAMILIES [J].
CORDER, EH ;
SAUNDERS, AM ;
STRITTMATTER, WJ ;
SCHMECHEL, DE ;
GASKELL, PC ;
SMALL, GW ;
ROSES, AD ;
HAINES, JL ;
PERICAKVANCE, MA .
SCIENCE, 1993, 261 (5123) :921-923