From aging to Alzheimer's disease: unveiling "the switch" with the senescence-accelerated mouse model (SAMP8).
Current mouse models of Alzheimer's disease (AD) are restricted to the expression of AD-related pathology associated with specific mutations present in early-onset familial AD and thus represent < 5% of AD cases. To date there are no mouse lines that model late-onset/age-related AD, the feature which accounts for the vast majority of cases. As such, based on current mutation-associated models, the chronology of events that lead to the disease in the aged population is difficult to establish. However, published data show that senescence-accelerated mouse (SAMP8), as a model of aging, display many features that are known to occur early in the pathogenesis of AD such as increased oxidative stress, amyloid-beta alterations, and tau phosphorylation. Therefore, SAMP8 mice may be an excellent model for studying the earliest neurodegenerative changes associated with AD and provide a more encompassing picture of human disease, a syndrome triggered by a combination of age-related events. Here, the neurochemical, neuropathological, and behavioral alterations, characterized in SAMP8 mice are critically reviewed and discussed in relation to the potential use of this mouse model in the study of AD pathogenesis.
Pallas
Merce
M
Unitat de Farmacologia, Facultat de Farmàcia Institut de Biomedicina Universitat de Barcelona (IBUB), Nucli Universitari de Pedralbes, Barcelona, Spain.
Camins
Antoni
A
Smith
Mark A
MA
Perry
George
G
Lee
Hyoung-gon
HG
Casadesus
Gemma
G
D000375:Aging / Q000235:genetics* / Q000473:pathology*; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000235:genetics; D000818:Animals; D003071:Cognition / Q000502:physiology; D005911:Gliosis / Q000235:genetics / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000502:physiology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016875:tau Proteins