Tau45-230 association with the cytoskeleton and membrane-bound organelles: Functional implications in

Sana Afreen1, D Nicole Riherd Methner1, Adriana Ferreira1

  • 1Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Neuroscience
|August 28, 2017
PubMed

Insights

The tau45-230 fragment, linked to Alzheimer's disease, disrupts axonal transport in neurons. This disruption, caused by tau cleavage, contributes to early Alzheimer's pathology.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Posttranslational modifications of microtubule-associated protein (MAP) tau are implicated in Alzheimer's disease (AD).
  • Beta-amyloid (Aβ) induces neurotoxicity partly via tau cleavage into the tau45-230 fragment.
  • The precise mechanisms of tau45-230 toxicity remain unclear.

Purpose of the Study:

  • To investigate the subcellular localization of the tau45-230 fragment in hippocampal neurons.
  • To determine the impact of tau45-230 on axonal transport.
  • To elucidate the contribution of tau45-230 to early Alzheimer's disease pathology.

Main Methods:

  • Subcellular localization studies using cell extraction with Triton X-100 and saponin in cultured hippocampal neurons.
  • Assessment of axonal transport in hippocampal neurons treated with tau45-230.
  • Analysis of organelle counts and motor protein levels.

Main Results:

  • Tau45-230 was detected in the cell bodies and processes of hippocampal neurons.
  • A portion of tau45-230 associated with the cytoskeleton and cytoskeleton plus membrane-bound organelles, independently of full-length tau.
  • Tau45-230 significantly reduced axonal transport of organelles without altering total organelle numbers or motor protein levels.

Conclusions:

  • The tau45-230 fragment localizes within hippocampal neurons and associates with cellular structures.
  • Tau45-230 impairs axonal transport by partially blocking microtubule function.
  • These findings suggest tau45-230 contributes to early Alzheimer's disease pathogenesis through axonal transport disruption.

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