Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice

Paul F. Chapman, Gail L. White, Matthew W. Jones, Deirdre Cooper-Blacketer, Vanessa J. Marshall, Michael Irizarry, Linda Younkin, Mark A. Good, T. V.P. Bliss, Bradley T. Hyman, Steven G. Younkin, Karen K. Hsiao

Research output: Contribution to journalArticlepeer-review

784 Scopus citations


We investigated synaptic communication and plasticity in hippocampal slices from mice overexpressing mutated 695-amino-acid human amyloid precursor protein (APP695SWE), which show behavioral and histopathological abnormalities simulating Alzheimer's disease. Although aged APP transgenic mice exhibit normal fast synaptic transmission and short term plasticity, they are severely impaired in in-vitro and in-vivo long-term potentiation (LTP) in both the CA1 and dentate gyrus regions of the hippocampus. The LTP deficit was correlated with impaired performance in a spatial working memory task in aged transgenics. These deficits are accompanied by minimal or no loss of presynaptic or postsynaptic elementary structural elements in the hippocampus, suggesting that impairments in functional synaptic plasticity may underlie some of the cognitive deficits in these mice and, possibly, in Alzheimer's patients.

Original languageEnglish (US)
Pages (from-to)271-276
Number of pages6
JournalNature Neuroscience
Issue number3
StatePublished - Mar 1999

ASJC Scopus subject areas

  • Neuroscience(all)


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