Alteration of cortical EEG in mice carrying mutated human APP transgene

Brain Res. 2002 Jul 12;943(2):181-90. doi: 10.1016/s0006-8993(02)02617-3.

Abstract

Transgenic mice expressing human APPswe and PS1-A264E mutations mimic certain neuropathological features of Alzheimer's disease (AD). These mice have elevated levels of the highly fibrillogenic amyloid beta1-42 peptide (Abeta42) and develop amyloid plaques around the age of 9 months. Our aim was to find whether these transgenic mice differ electrophysiologically from non-transgenic mice and whether the alteration in EEG activity progresses with the accumulation of Abeta. The APP/PS1 mice had reduced cortical theta activity and enhanced beta and gamma activity, but these changes were not age-dependent. APP single mutant mice had similar EEG alterations in theta, beta and gamma bands as APP/PS1 double mutant mice while PS1 single mutant mice did not differ from non-transgenic controls. Insoluble Abeta40 and Abeta42 levels were robustly increased in APP/PS1 double mutant mice and insoluble Abeta40 moderately increased also in APP single mutant mice. Soluble Abeta42 was found in all APP mutant mice but also in lower concentrations in PS1 single mutant mice. Plaques were deposited in 13-month-old APP/PS1 double mutant mice but not in 8-month-old double mutant or 13-month-old single mutant mice. We conclude that the alteration of EEG activity in APP/PS1 double mutant and APP single mutant mice is related to their APP genotype rather than to deposition of beta-amyloid in the brain.

Publication types

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

MeSH terms

  • Action Potentials / genetics
  • Age Factors
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / genetics*
  • Amyloid beta-Protein Precursor / deficiency*
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Cerebral Cortex / pathology
  • Cerebral Cortex / physiopathology*
  • Electroencephalography
  • Genotype
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Mice
  • Mice, Transgenic
  • Mutation / genetics
  • Neurons / pathology
  • Peptide Fragments / genetics
  • Plaque, Amyloid / genetics
  • 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 (1-40)
  • amyloid beta-protein (1-42)