Correlation between cognitive deficits and Abeta deposits in transgenic APP+PS1 mice

Neurobiol Aging. May-Jun 2001;22(3):377-85. doi: 10.1016/s0197-4580(00)00249-9.

Abstract

Doubly transgenic mAPP+mPS1 mice (15-16 months) had impaired cognitive function in a spatial learning and memory task that combined features of a water maze and a radial arm maze. Nontransgenic mice learned a new platform location each day during 4 consecutive acquisition trials, and exhibited memory for this location in a retention trial administered 30 min later. In contrast, transgenic mice were, on average, unable to improve their performance in finding the hidden platform over trials. The cognitive performance of individual mice within the transgenic group were inversely related to the amount of Abeta deposited in the frontal cortex and hippocampus. These findings imply that mAPP+mPS1 transgenic mice develop deficits in cognitive ability as Abeta deposits increase. These data argue that radial arm water maze testing of doubly transgenic mice may be a useful behavioral endpoint in evaluating the functional consequences of potential AD therapies, especially those designed to reduce Abeta load.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Amino Acid Substitution / genetics
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / genetics*
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Female
  • Frontal Lobe / metabolism
  • Frontal Lobe / pathology
  • Frontal Lobe / physiopathology
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Immunohistochemistry
  • Male
  • Maze Learning / physiology
  • Membrane Proteins / genetics*
  • Memory / physiology
  • Mice
  • Mice, Transgenic
  • Mutation / genetics
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology*
  • Neurodegenerative Diseases / physiopathology*
  • Peptide Fragments / metabolism
  • Plaque, Amyloid / genetics*
  • Plaque, Amyloid / metabolism*
  • Plaque, Amyloid / pathology
  • Presenilin-1
  • Space Perception / physiology

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Membrane Proteins
  • Peptide Fragments
  • Presenilin-1
  • amyloid beta-protein (1-40)