title: 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.
authors: Cardiff School of Biosciences, Cardiff University, Wales, UK.
authors: P F
authors: PF
authors: Chapman
authors: G L
authors: GL
authors: White
authors: M W
authors: MW
authors: Jones
authors: D
authors: D
authors: Cooper-Blacketer
authors: V J
authors: VJ
authors: Marshall
authors: M
authors: M
authors: Irizarry
authors: L
authors: L
authors: Younkin
authors: M A
authors: MA
authors: Good
authors: T V
authors: TV
authors: Bliss
authors: B T
authors: BT
authors: Hyman
authors: S G
authors: SG
authors: Younkin
authors: K K
authors: KK
authors: Hsiao
mesh_terms: D000375:Aging / Q000502:physiology* / Q000523:psychology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018891:Dentate Gyrus / Q000502:physiology; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology; D008568:Memory / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009473:Neuronal Plasticity / Q000502:physiology*; D013028:Space Perception / Q000502:physiology; D013569:Synapses / Q000502:physiology*
chemical_list: D016564:Amyloid beta-Protein Precursor