Impairments in remote memory stabilization precede hippocampal synaptic and cognitive failures in 5XFAD Alzheimer mouse model

Neurobiol Dis. 2009 Feb;33(2):229-35. doi: 10.1016/j.nbd.2008.10.006. Epub 2008 Nov 5.


Although animal models of Alzheimer's disease (AD) recapitulate beta-amyloid-dependent hippocampal synaptic and cognitive dysfunctions, it is poorly understood how cortex-dependent remote memory stabilization following initial hippocampal coding is affected. Here, we systematically analyzed biophysical and behavioral phenotypes, including remote memory functions, of 5XFAD APP/PS1 transgenic mice containing five familial AD mutations. We found that 5XFAD mice show hippocampal dysfunctions as observed by reduced levels of baseline transmission and long-term potentiation at Schaffer collateral-CA1 synapses. Hippocampus-dependent memory tested 1 day after contextual fear conditioning was also impaired age-dependently in 5XFAD mice, as correlated with the onset of hippocampal synaptic failures. Importantly, remote memory stabilization during 30 days after training significantly declined in 5XFAD mice at time well before the onset of hippocampal dysfunctions. Our results indicate that 5XFAD mice provide a useful model system to investigate the mechanisms and therapeutic interventions for multiple synaptic and memory dysfunctions associated with AD.

Publication types

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

MeSH terms

  • Age Factors
  • Alzheimer Disease / physiopathology*
  • Alzheimer Disease / psychology
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Conditioning, Psychological
  • Disease Models, Animal*
  • Excitatory Postsynaptic Potentials
  • Extinction, Psychological / physiology
  • Fear / psychology
  • Hippocampus / physiopathology*
  • Humans
  • Long-Term Potentiation*
  • Memory / physiology*
  • Mice
  • Mice, Transgenic
  • Mutation
  • Presenilin-1 / genetics
  • Protease Nexins
  • Receptors, Cell Surface / genetics
  • Synaptic Transmission*


  • APP protein, human
  • Amyloid beta-Protein Precursor
  • Presenilin-1
  • Protease Nexins
  • Receptors, Cell Surface