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Neurodegenerative diseases

Mighty mouse

Nature Reviews Neuroscience volume 4, page 701 (2003)Cite this article

Murine models that exhibit one of the pathological lesions that characterize Alzheimer's disease have been available for some time. Now, the first triple transgenic mouse to develop both amyloid-β (Aβ) plaques and tangles of hyperphosphorylated tau protein in AD-relevant brain regions has been unveiled in the 31 July issue of Neuron.

Frank LaFerla's team used microinjection of single-cell embryos — rather than standard cross-breeding techniques — to create mice harbouring transgenes that encode mutant forms of human amyloid precursor protein (APP), tau and presenilin-1. Immunohistochemistry revealed that the hippocampus and cerebral cortex of the triple-transgenics contained high steady-state levels of both human tau and APP, which was processed to form Aβ in an age-dependent manner. Deposition of extracellular Aβ preceded the formation of tau tangles, lending weight to the amyloid cascade hypothesis, which predicts that Aβ is the initiating trigger for the formation of tangles and the onset of Alzheimer's disease.

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References

ORIGINAL RESEARCH PAPER

  1. Oddo, S. et al. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Aβ and synaptic dysfunction. Neuron 39, 409–421 (2003)

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FURTHER READING

  1. Wong, P. C. et al. Genetically engineered mouse models of neurodegenerative diseases. Nature Neurosci. 5, 633–639 (2002)

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Authors
  1. Suzanne Farley
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Farley, S. Mighty mouse. Nat Rev Neurosci 4, 701 (2003). https://doi.org/10.1038/nrn1215

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  • DOI: https://doi.org/10.1038/nrn1215

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