Are tangles as toxic as they look?

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

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)438-44
Number of pages7
JournalJournal of Molecular Neuroscience
Volume45
Issue number3
DOIs
Publication statusPublished - Nov 2011

Keywords

  • Alzheimer Disease
  • Animals
  • Brain
  • Cell Death
  • Humans
  • Neurofibrillary Tangles
  • Neurons
  • Tauopathies
  • tau Proteins

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