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Loss of tau elicits axonal degeneration in a mouse model of Alzheimer's disease.

Publication ,  Journal Article
Dawson, HN; Cantillana, V; Jansen, M; Wang, H; Vitek, MP; Wilcock, DM; Lynch, JR; Laskowitz, DT
Published in: Neuroscience
August 11, 2010

A central issue in the pathogenesis of tauopathy is the question of how tau protein dysfunction leads to neurodegeneration. We have previously demonstrated that the absence of tau protein is associated with destabilization of microtubules and impaired neurite outgrowth (Dawson et al., 2001; Rapoport et al., 2002). We now hypothesize that the absence of functional tau protein may render the central nervous system more vulnerable to secondary insults such as the overexpression of mutated beta amyloid precursor protein (APP) and traumatic brain injury. We therefore crossed tau knockout mice (Dawson et al., 2001) to mice overexpressing a mutated human APP (APP(670,671), A(sw)) (Hsiao et al., 1996) and created a mouse model (A(sw)/mTau(-/-)) that provides evidence that the loss of tau function causes degeneration of neuronal processes. The overexpression of APP(670,671) in tau knockout mice, elicits the extensive formation of axonal spheroids. While spheroids are only found associated with Abeta plaques in mice expressing APP(670,671) on an endogenous mouse tau background (Irizarry et al., 1997), A(sw)/mTau(-/-) mice have spheroids not only surrounding Abeta plaques but also in white matter tracks and in the neuropil. Plaque associated and neuropil dystrophic neurites and spheroids are prominent features of Alzheimer's disease (Masliah et al., 1993; Terry, 1996; Stokin et al., 2005), and our current data suggests that loss of tau function may lead to neurodegeneration.

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Published In

Neuroscience

DOI

EISSN

1873-7544

Publication Date

August 11, 2010

Volume

169

Issue

1

Start / End Page

516 / 531

Location

United States

Related Subject Headings

  • tau Proteins
  • Recombinant Fusion Proteins
  • Plaque, Amyloid
  • Neuropil
  • Neurology & Neurosurgery
  • Neurites
  • Nerve Degeneration
  • Microscopy, Electron
  • Mice, Transgenic
  • Mice, Knockout
 

Citation

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Dawson, H. N., Cantillana, V., Jansen, M., Wang, H., Vitek, M. P., Wilcock, D. M., … Laskowitz, D. T. (2010). Loss of tau elicits axonal degeneration in a mouse model of Alzheimer's disease. Neuroscience, 169(1), 516–531. https://doi.org/10.1016/j.neuroscience.2010.04.037
Dawson, H. N., V. Cantillana, M. Jansen, H. Wang, M. P. Vitek, D. M. Wilcock, J. R. Lynch, and D. T. Laskowitz. “Loss of tau elicits axonal degeneration in a mouse model of Alzheimer's disease.Neuroscience 169, no. 1 (August 11, 2010): 516–31. https://doi.org/10.1016/j.neuroscience.2010.04.037.
Dawson HN, Cantillana V, Jansen M, Wang H, Vitek MP, Wilcock DM, et al. Loss of tau elicits axonal degeneration in a mouse model of Alzheimer's disease. Neuroscience. 2010 Aug 11;169(1):516–31.
Dawson, H. N., et al. “Loss of tau elicits axonal degeneration in a mouse model of Alzheimer's disease.Neuroscience, vol. 169, no. 1, Aug. 2010, pp. 516–31. Pubmed, doi:10.1016/j.neuroscience.2010.04.037.
Dawson HN, Cantillana V, Jansen M, Wang H, Vitek MP, Wilcock DM, Lynch JR, Laskowitz DT. Loss of tau elicits axonal degeneration in a mouse model of Alzheimer's disease. Neuroscience. 2010 Aug 11;169(1):516–531.
Journal cover image

Published In

Neuroscience

DOI

EISSN

1873-7544

Publication Date

August 11, 2010

Volume

169

Issue

1

Start / End Page

516 / 531

Location

United States

Related Subject Headings

  • tau Proteins
  • Recombinant Fusion Proteins
  • Plaque, Amyloid
  • Neuropil
  • Neurology & Neurosurgery
  • Neurites
  • Nerve Degeneration
  • Microscopy, Electron
  • Mice, Transgenic
  • Mice, Knockout