Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice
- 1 March 1999
- journal article
- research article
- Published by Springer Nature in Nature Neuroscience
- Vol. 2 (3), 271-276
- https://doi.org/10.1038/6374
Abstract
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.Keywords
This publication has 30 references indexed in Scilit:
- A New Pathogenic Mutation in the APP Gene (I716V) Increases the Relative Proportion of A 42(43)Human Molecular Genetics, 1997
- Familial Alzheimer's Disease–Linked Presenilin 1 Variants Elevate Aβ1–42/1–40 Ratio In Vitro and In VivoNeuron, 1996
- Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1Nature, 1996
- Release of Excess Amyloid β Protein from a Mutant Amyloid β Protein PrecursorScience, 1993
- Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein productionNature, 1992
- A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N–terminus of β–amyloidNature Genetics, 1992
- Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the β–amyloid precursor protein geneNature Genetics, 1992
- A mutation in the Amyloid Precursor Protein Associated with Hereditary Alzheimer's DiseaseScience, 1991
- Early-onset Alzheimer's disease caused by mutations at codon 717 of the β-amyloid precursor protein geneNature, 1991
- Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's diseaseNature, 1991