Deficits in working memory and motor performance in the APP/PS1ki mouse model for Alzheimer's disease

Neurobiol Aging. 2008 Jun;29(6):891-901. doi: 10.1016/j.neurobiolaging.2006.12.004. Epub 2007 Jan 9.

Abstract

The APP/PS1ki mouse model for Alzheimer's disease (AD) exhibits robust brain and spinal cord axonal degeneration and hippocampal CA1 neuron loss starting at 6 months of age. It expresses human mutant APP751 with the Swedish and London mutations together with two FAD-linked knocked-in mutations (PS1 M233T and PS1 L235P) in the murine PS1 gene. The present report covers a phenotypical analysis of this model using either behavioral tests for working memory and motor performance, as well as an analysis of weight development and body shape. At the age of 6 months, a dramatic, age-dependent change in all of these properties and characteristics was observed, accompanied by a significantly reduced ability to perform working memory and motor tasks. The APP/PS1ki mice were smaller and showed development of a thoracolumbar kyphosis, together with an incremental loss of body weight. While 2-month-old APP/PS1ki mice were inconspicuous in all of these tasks and properties, there is a massive age-related impairment in all tested behavioral paradigms. We have previously reported robust axonal degeneration in brain and spinal cord, as well as abundant hippocampal CA1 neuron loss starting at 6 months of age in the APP/PS1ki mouse model, which coincides with the onset of motor and memory deficits described in the present report.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / complications
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Protein Precursor / genetics*
  • Animals
  • Disease Models, Animal*
  • Female
  • Memory Disorders / complications
  • Memory Disorders / physiopathology*
  • Memory*
  • Mice
  • Mice, Transgenic
  • Psychomotor Performance*

Substances

  • Amyloid beta-Protein Precursor