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International Journal of Alzheimer’s Disease
Volume 2017 (2017), Article ID 8584205, 7 pages
https://doi.org/10.1155/2017/8584205
Research Article

Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-β Precursor Protein/Presenilin 2 Mouse Model of Alzheimer’s Disease

Laboratory of Neurobiophysics, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan

Correspondence should be addressed to Yasushi Kishimoto; pj.ca.u-irnub.hpk@tomihsik

Received 29 August 2017; Revised 31 October 2017; Accepted 6 November 2017; Published 27 November 2017

Academic Editor: Jeff Kuret

Copyright © 2017 Yasushi Kishimoto et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Presenilin 1 and presenilin 2 (PS1 and PS2) play a critical role in γ-secretase-mediated cleavage of amyloid-β precursor protein (APP) and the subsequent generation of β-amyloid peptides. The purpose of the present study was to test whether PS2 mutation accelerates the onset of contextual fear memory deficits in a mouse model of AD that expresses a mutation (K670N/M671L) of the human APP with the Swedish mutation (Tg2576 mice). In the present study, an APP/PS2 double-transgenic mouse model (PS2Tg2576) was generated by crossbreeding transgenic mice carrying the human mutant PS2 (N141I) with Tg2576 mice. Contextual fear conditioning was tested in PS2Tg2576 mice aged 3, 4, 6, and 10–12 months. PS2Tg2576 mice showed a tendency of lower freezing behavior as early as 3 months of age, but significant memory impairment was observed from the age of 4 months. The cognitive impairment was more prominent at ages of 6 and 10–12 months. In contrast, Tg2576 mice aged 3 and 4 months exhibited successful acquisition of contextual fear learning, but Tg2576 mice aged 6 months or older showed significantly impaired fear memory. These results show that PS2 mutation significantly accelerates the onset of fear memory deficits in the APP AD model mice.