title: Characterization of the APP/PS1 mouse model of Alzheimer's disease in senescence accelerated background.
abstract: The APP/PS1 mouse model of Alzheimer's disease (AD) exhibits remarkable elevation of β-amyloid production associated with certain behavioral abnormalities, while the senescence accelerated mouse prone 8 (SAMP8) is characterized by early and age-related deterioration of learning and memory. In order to obtain an AD model that develops earlier pathological changes and cognitive impairment, we generated SAMP8-APP/PS1, a novel senescence accelerated APP/PS1 transgenic mouse model of AD. Standard histological staining and immunohistochemistry using an amyloid beta (Aβ) antibody showed an age, genotype and strain-dependent progression of amyloid deposition and neuron loss in the cerebral cortex and hippocampus of SAMP8-APP/PS1 mice. Results from the cognitive behavioral tests revealed early deficits in learning and memory in SAMP8-APP/PS1 mice in the two way active avoidance and Morris water maze tests compared with C57-APP/PS1, SAMP8 wild-type and control mice. These results suggest that accelerated senescence exacerbates amyloid deposition and cognitive dysfunction in APP/PS1 mice and the senescence accelerated-APP/PS1 (SAMP8-APP/PS1) mouse model might be a valuable tool to study AD progression and to evaluate the effect of drugs on AD.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Kenghoe
authors.initials: K
authors.lastname: Lok
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Hanlin
authors.initials: H
authors.lastname: Shen
authors.forename: Zejian
authors.initials: Z
authors.lastname: Wang
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Zhao
authors.forename: Ming
authors.initials: M
authors.lastname: Yin
mesh_terms: D000375:Aging / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1
keywords: APP/PS1; Amyloid β; Memory impairment; SAMP8