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Journal of Biomedicine and Biotechnology
Volume 2011 (2011), Article ID 617974, 12 pages
http://dx.doi.org/10.1155/2011/617974
Research Article

Presenilin-2 Mutation Causes Early Amyloid Accumulation and Memory Impairment in a Transgenic Mouse Model of Alzheimer's Disease

1Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-Cho, Itabashi-Ku, Tokyo 173-0015, Japan
2JAC Co, Ltd, 1-2-7 Higashiyama, Meguro-Ku, Tokyo 153-0043, Japan
3Immuno-Biological Laboratories Co, Ltd., 1091-1 Naka, Aza-Higashida, Fujioka-shi, Gunma 370-0831, Japan

Received 15 September 2010; Revised 17 November 2010; Accepted 4 December 2010

Academic Editor: Monica Fedele

Copyright © 2011 Toshihiko Toda 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

In order to clarify the pathophysiological role of presenilin-2 (PS2) carrying the Volga German Kindred mutation (N141I) in a conventional mouse model of Alzheimer's disease (AD) expressing amyloid precursor protein (APP) with the Swedish mutation (Tg2576 line), we generated a double transgenic mouse (PS2Tg2576) by crossbreeding the PS2 mutant with Tg2576 mice. Here, we demonstrate that the PS2 mutation induced the early deposition of amyloid β-protein (Aβ) at 2-3 months of age and progressive accumulation at 4-5 months of age in the brains of the mutant mice. The PS2 mutation also accelerated learning and memory impairment associated with Aβ accumulation at 4-5 months of age in Tg2576 mice. These results suggest that the PS2 mutation causes early cerebral amyloid accumulation and memory dysfunction. PS2Tg2576 mice are a suitable mouse model for studying amyloid-lowering therapies.