• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction.

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.

Pubmed ID: 12895417

Authors

  • Oddo S
  • Caccamo A
  • Shepherd JD
  • Murphy MP
  • Golde TE
  • Kayed R
  • Metherate R
  • Mattson MP
  • Akbari Y
  • LaFerla FM

Journal

Neuron

Publication Data

July 31, 2003

Associated Grants

  • Agency: NIA NIH HHS, Id: AG17968

Mesh Terms

  • Alzheimer Disease
  • Amyloid beta-Peptides
  • Animals
  • Disease Models, Animal
  • Humans
  • Intracellular Fluid
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurofibrillary Tangles
  • Plaque, Amyloid
  • Synapses