References
Query Results -- Details
MGI Accession ID: MGI:2670324
J Number: J:84847
Other Accession IDs:
Title: Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction.
Authors: Oddo S; Caccamo A; Shepherd JD; Murphy MP; Golde TE; Kayed R; Metherate R; Mattson MP; Akbari Y; LaFerla FM
Journal: Neuron
Volume: 39
Issue: 3
Date: 2003 Jul 31
Year: 2003
Pages: 409-21
Review Status: Peer Reviewed
Abstract:
The neuropathological correlates of Alzheimer's disease (AD) include amyloid-beta (Abeta) plaques and neurofibrillary tangles. To study the interaction between Abeta and tau and their effect on synaptic function, we derived a triple-transgenic model (3xTg-AD) harboring PS1(M146V), APP(Swe), and tau(P301L) transgenes. Rather than crossing independent lines, we microinjected two transgenes into single-cell embryos from homozygous PS1(M146V) knockin mice, generating mice with the same genetic background. 3xTg-AD mice progressively develop plaques and tangles. Synaptic dysfunction, including LTP deficits, manifests in an age-related manner, but before plaque and tangle pathology. Deficits in long-term synaptic plasticity correlate with the accumulation of intraneuronal Abeta. These studies suggest a novel pathogenic role for intraneuronal Abeta with regards to synaptic plasticity. The recapitulation of salient features of AD in these mice clarifies the relationships between Abeta, synaptic dysfunction, and tangles and provides a valuable model for evaluating potential AD therapeutics as the impact on both lesions can be assessed.
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