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 H Ashe

Research output: Contribution to journalArticlepeer-review


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
Externally publishedYes

Bibliographical note

Funding Information:
The authors acknowledge the NIH (NS33249 (KH), K08-AG00793 (MI and BH), and AG08487 (BH)), the Mayo Medical Foundation (KH, SY) and the Medical Research Council (PC).


Dive into the research topics of 'Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice'. Together they form a unique fingerprint.

Cite this