Presenilin-2 Mutation Causes Early Amyloid Accumulation and Memory Impairment in a Transgenic Mouse Model of Alzheimer's Disease
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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Hindawi Limited
2011-01-01
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| Series: | Journal of Biomedicine and Biotechnology |
| Online Access: | http://dx.doi.org/10.1155/2011/617974 |
| Summary: | 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. |
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| ISSN: | 1110-7243 1110-7251 |