Hippocampal A beta 42 levels correlate with spatial memory deficit in APP and PS1 double transgenic mice

Neurobiol Dis. 2002 Apr;9(3):339-47. doi: 10.1006/nbdi.2002.0481.

Abstract

We investigated the role of hippocampal amyloid pathology in spatial learning impairment of a new mouse line carrying mutated human amyloid precursor protein (APP) and presenilin-1 (PS1) transgenes. The APP + PS1 mice were tested in spatial navigation in the water maze and in position discrimination in the T-maze at ages of 3-4 and 11-12 months, before and after the appearance of first amyloid plaques. The APP + PS1 mice were impaired in water maze acquisition and retention only at the age of 11-12 months, but performed equally to controls in the T-maze task at both ages. In the impaired older age group, the levels of total Abeta1-42 in the hippocampus of APP + PS1 mice correlated negatively with the retention score. Here we show for the first time that the age-dependent impairment in memory retention in the traditional water maze of APP + PS1 mice correlates with the amount of total Abeta in hippocampus even at a stage when the amyloid deposits cover less than 1% of the hippocampal volume.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / genetics*
  • Animals
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Memory Disorders / genetics*
  • Memory Disorders / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism*
  • Plaque, Amyloid / genetics
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology
  • Presenilin-1

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Membrane Proteins
  • PSEN1 protein, human
  • Peptide Fragments
  • Presenilin-1
  • amyloid beta-protein (1-42)