Presenilin-2 mutation causes early amyloid accumulation and memory impairment in a transgenic mouse model of Alzheimer's disease

J Biomed Biotechnol. 2011:2011:617974. doi: 10.1155/2011/617974. Epub 2010 Dec 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Amyloid / metabolism*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Blotting, Western
  • Brain / metabolism
  • Brain / pathology
  • Disease Models, Animal
  • Female
  • Kaplan-Meier Estimate
  • Longevity
  • Male
  • Maze Learning
  • Memory Disorders / genetics*
  • Mice
  • Mice, Transgenic
  • Mutation / genetics*
  • Phenotype
  • Presenilin-2 / genetics*
  • Solubility

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Presenilin-2