Loss of tau elicits axonal degeneration in a mouse model of Alzheimer's disease.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Dawson, HN; Cantillana, V; Jansen, M; Wang, H; Vitek, MP; Wilcock, DM; Lynch, JR; Laskowitz, DT
Published Date
- August 11, 2010
Published In
Volume / Issue
- 169 / 1
Start / End Page
- 516 - 531
PubMed ID
- 20434528
Pubmed Central ID
- PMC2900546
Electronic International Standard Serial Number (EISSN)
- 1873-7544
Digital Object Identifier (DOI)
- 10.1016/j.neuroscience.2010.04.037
Language
- eng
Conference Location
- United States