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Brain Res. 2001 Feb 9;891(1-2):42-53.

Progressive, age-related behavioral impairments in transgenic mice carrying both mutant amyloid precursor protein and presenilin-1 transgenes.

Author information

1
Alzheimer's Research Laboratory, Department of Biology, University of South Florida, Tampa, FL 33620, USA. arendash@chuma.cas.usf.edu

Abstract

This study provides a comprehensive behavioral characterization during aging of transgenic mice bearing both presenilin-1 (PS1) and amyloid precursor protein (APP(670,671)) mutations. Doubly transgenic mice and non-transgenic controls were evaluated at ages wherein beta-amyloid (Abeta) neuropathology in APP+PS1 mice is low (5-7 months) or very extensive (15-17 months). Progressive cognitive impairment was observed in transgenic mice for both water maze acquisition and radial arm water maze working memory. However, transgenicity did not affect Y-maze alternations, circular platform performance, standard water maze retention, or visible platform recognition at either age, nor did transgenicity affect anxiety levels in elevated plus-maze testing. In sensorimotor tasks, transgenic mice showed a progressive increase in open field activity, a progressive impairment in string agility, and an early-onset impairment in balance beam. None of these sensorimotor changes appeared to be contributory to any cognitive impairments observed, however. Non-transgenic mice showed no progressive behavioral change in any measure evaluated. Given the age-related cognitive impairments presently observed in APP+PS1 transgenic mice and their progressive Abeta deposition/neuroinflammation, Abeta neuropathology could be involved in these progressive cognitive impairments. As such, the APP+PS1 transgenic mouse offers unique opportunities to develop therapeutics to treat or prevent Alzheimer's Disease through modulation of Abeta deposition/neuroinflammation.

PMID:
11164808
DOI:
10.1016/s0006-8993(00)03186-3
[Indexed for MEDLINE]

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