Associative and motor learning in 12-month-old transgenic APP+PS1 mice

Neurobiol Aging. 2006 Aug;27(8):1118-28. doi: 10.1016/j.neurobiolaging.2005.05.019. Epub 2005 Jul 1.

Abstract

Doubly transgenic 12-month-old amyloid precursor protein and presenilins 1 (APP+PS1) mice (n=14) and littermate control mice (n=17) were tested on eyeblink classical conditioning-a task impaired in humans with Alzheimer's disease (AD). Mice were also tested on a motor learning task (rotorod) and on sensory tasks (prepulse inhibition [PPI] and acoustic startle). Transgenic mice had impaired motor performance on rotorod. Overall, APP+PS1 mice performed similarly to controls on both 500ms delay and 500ms trace eyeblink conditioning as well as on prepulse inhibition (PPI) and acoustic startle. However, within the transgenic group, cortical amyloid burden correlated significantly with decreased trace eyeblink conditioning. Moreover, cortical amyloid burden and hippocampal microglia activation correlated significantly with decreased PPI. These data suggest that only those transgenic mice with the most severe amyloid pathology exhibited deficits in hippocampus-dependent tasks. Transgenic mouse models of amyloid deposition differ from Alzheimer patients not only by the absence of major neuronal loss, but also by the general absence of severe impairments in eyeblink conditioning, except for mice with the greatest amyloid pathology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Association Learning*
  • Conditioning, Classical*
  • Disease Models, Animal*
  • Female
  • Male
  • Mice
  • Mice, Transgenic
  • Motor Skills*
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism*
  • Task Performance and Analysis

Substances

  • Amyloid beta-Peptides
  • Presenilin-1