From Aging to Alzheimer's Disease: Unveiling “The Switch” with the Senescence-Accelerated Mouse Model (SAMP8)

Issue title: Animal Models of Alzheimer's Disease: Therapeutic Implications

Guest editors: Diana Woodruff-Pak

Article type: Research Article

Authors: Pallas, Merce^a | Camins, Antoni^a | Smith, Mark A.^b | Perry, George^{b; c} | Lee, Hyoung-gon^b | Casadesus, Gemma^{d; *}

Affiliations: [a] Unitat de Farmacologia, Facultat de Farmàcia Institut de Biomedicina Universitat de Barcelona (IBUB), Nucli Universitari de Pedralbes, Barcelona, Spain | [b] Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA | [c] College of Sciences, University of Texas at San Antonio, San Antonio, TX, USA | [d] Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio, USA

Correspondence: [*] Corresponding author: Gemma Casadesus, Ph.D., Case Western Reserve University, 2109 Adelbert Road, Cleveland, OH 44106, USA. Tel.: +1 216 368 8503; E-mail: [email protected].

Abstract: 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-β 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.

Keywords: Aging, Alzheimer's disease, amyloid-β, animal models, cognition, gliosis, neurodegeneration, oxidative stress, SAMP8, tau phosphorylation

DOI: 10.3233/JAD-2008-15408

Journal: Journal of Alzheimer's Disease, vol. 15, no. 4, pp. 615-624, 2008