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Journal of Molecular Neuroscience

, Volume 45, Issue 3, pp 438–444 | Cite as

Are Tangles as Toxic as They Look?

  • Tara L. Spires-Jones
  • Katherine J. Kopeikina
  • Robert M. Koffie
  • Alix de Calignon
  • Bradley T. Hyman
Article

Abstract

Neurofibrillary tangles are intracellular accumulations of hyperphosphorylated and misfolded tau protein characteristic of Alzheimer’s disease and other tauopathies. Classic cross-sectional studies of Alzheimer patient brains showed associations of tangle accumulation with neuronal loss, synapse loss, and dementia, which led to the supposition that tangles are toxic to neurons. More recent advances in imaging techniques and mouse models have allowed the direct exploration of the question of toxicity of aggregated versus soluble tau and have surprisingly challenged the view of tangles as toxic species in the brain. Here, we review these recent experiments on the nature of the toxicity of tau with particular emphasis on our experiments imaging tangles in the intact brain through a cranial window, which allows observation of tangle formation and longitudinal imaging of the fate of tangle-bearing neurons.

Keywords

Tau Alzheimer Neurofibrillary tangle Neurodegeneration 

Notes

Acknowledgements

This work was supported by National Institute of Health grants AG08487, T32AG000278, AG026249, K99AG33670 and the Alzheimer's Association Zenith Award.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Tara L. Spires-Jones
    • 1
  • Katherine J. Kopeikina
    • 1
    • 2
  • Robert M. Koffie
    • 1
  • Alix de Calignon
    • 3
  • Bradley T. Hyman
    • 1
  1. 1.Massachusetts General Hospital, Harvard Medical SchoolCharlestownUSA
  2. 2.Department of Anatomy and NeurobiologyBoston University School of MedicineBostonUSA
  3. 3.Department of Physiology, Anatomy, and GeneticsUniversity of OxfordOxfordUK

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