Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice
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.
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Tg2576 mice develop age-dependent behavioral deficits as assessed by Y maze, T maze, and Morris water maze testing.
“In addition, Tg2576 mice develop agedependent behavioral deficits as assessed by Y maze, T maze, and Morris water maze testing (Hsiao et al., 1996;Chapman et al., 1999;Westerman et al., 2000).”
From Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease (2001) · cites this paper as Chapman et al., 1999
AD transgenic mice showed physiological and neuritic alterations prior to plaques.
“AD transgenic mice showed physiological [32, 74, 77, 124] and neuritic alterations [22, 125] prior to plaques”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [32]
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References 33 · Cited by 946
- Authors
- Chapman, P. F., White, G. L., Jones, M. W., Cooper-Blacketer, D., Marshall, V. J., Irizarry, M., Younkin, L., Good, M. A., Bliss, T. V. P., Hyman, B. T., Younkin, S. G., & Hsiao, K. K.
- Affiliations
- Cardiff University (GB)
- National Institute for Medical Research (GB)
- University of Minnesota (US)
- Massachusetts General Hospital (US)
- Mayo Clinic in Florida (US)
- Corresponding author
- Hsiao, Karen K.
- ORCID
- Venue
- Nature Neuroscience
- Published
- 1999-03
- Volume
- 2
- Issue
- 3
- Pages
- 271-276
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- DOI
- 10.1038/6374
- OpenAlex
- W1886575365
- Cited by
- 946
- References
- 33
- Citations by year
- 2026: 14 · 2025: 18 · 2024: 20 · 2023: 12 · 2022: 15 · 2021: 20 · 2020: 32 · 2019: 24 · 2018: 21 · 2017: 33 · 2016: 33 · 2015: 38 · 2014: 27 · 2013: 39 · 2012: 49
- FWCI
- 25.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Funders
- National Institutes of Health (5k08ag000793-05)
- National Institute on Aging (AG-08487, K08 AG00793)
- National Institute of Neurological Disorders and Stroke (NS33249, R01NS033249)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- amyloid precursor protein, Alzheimer's disease, synaptic plasticity, long-term potentiation, hippocampus, aging, spatial working memory, synaptic transmission, CA1, dentate gyrus, learning deficits
- MeSH terms
- Aging, Animals, Hippocampus, Humans, Learning, Memory, Mice, Transgenic, Neuronal Plasticity, Space Perception, Synapses, Amyloid beta-Protein Precursor, Long-Term Potentiation, Dentate Gyrus, Mice
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