Progressive, age-related behavioral impairments in transgenic mice carrying both mutant amyloid precursor protein and presenilin-1 transgenes.
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.
Arendash
G W
GW
Alzheimer's Research Laboratory, Department of Biology, University of South Florida, Tampa, FL 33620, USA. arendash@chuma.cas.usf.edu
King
D L
DL
Gordon
M N
MN
Morgan
D
D
Hatcher
J M
JM
Hope
C E
CE
Diamond
D M
DM
D000375:Aging / Q000473:pathology / Q000502:physiology*; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003072:Cognition Disorders / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic / Q000502:physiology*; D009069:Movement Disorders / Q000235:genetics / Q000503:physiopathology; D009154:Mutation / Q000502:physiology; D004856:Postural Balance / Q000502:physiology; D053764:Presenilin-1; D011597:Psychomotor Performance / Q000502:physiology
D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; D053764:Presenilin-1