Amyloid-β and tau — a toxic pas de deux in Alzheimer's disease

Abstract

Amyloid-β and tau are the two hallmark proteins in Alzheimer's disease. Although both amyloid-β and tau have been extensively studied individually with regard to their separate modes of toxicity, more recently new light has been shed on their possible interactions and synergistic effects in Alzheimer's disease. Here, we review novel findings that have shifted our understanding of the role of tau in the pathogenesis of Alzheimer's disease towards being a crucial partner of amyloid-β. As we gain a deeper understanding of the different cellular functions of tau, the focus shifts from the axon, where tau has a principal role as a microtubule-associated protein, to the dendrite, where it mediates amyloid-β toxicity.

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Figure 1: Disrupting tau-dependent dendritic targeting of FYN protects neurons from amyloid-β toxicity in mouse models of Alzheimer's disease.
Figure 2: Amyloid-β and tau: three possible modes of interaction.
Figure 3: Proposed 'tau axis hypothesis' of Alzheimer's disease: progressively increasing levels of dendritic tau make neurons vulnerable to amyloid-β.

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Acknowledgements

This work has been supported by the University of Sydney, the National Health & Medical Research Council (NHMRC), the Australian Research Council (ARC) and the J.O. & J.R. Wicking Trust.

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Correspondence to Lars M. Ittner or Jürgen Götz.

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Alzheimer's and Parkinson's Disease Laboratory

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Ittner, L., Götz, J. Amyloid-β and tau — a toxic pas de deux in Alzheimer's disease. Nat Rev Neurosci 12, 67–72 (2011). https://doi.org/10.1038/nrn2967

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