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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
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The Way of Tau: Secretion and Synaptic Dysfunction.

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Researchers discovered a new tau protein secretion pathway and its uptake. Tau from Down syndrome models impaired rat synapses, suggesting new therapeutic targets for neurodegenerative diseases like Alzheimer's.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Tau protein is implicated in neurodegenerative diseases, notably Alzheimer's disease (AD).
  • Understanding tau's extracellular behavior is crucial for developing effective treatments.

Purpose of the Study:

  • To elucidate novel mechanisms of tau secretion and cellular uptake.
  • To investigate the impact of tau from specific disease models on neuronal function.

Main Methods:

  • Investigated a newly identified pathway for tau protein secretion.
  • Utilized human induced pluripotent stem cells (iPSCs) modeling trisomy 21-related AD.
  • Assessed synaptic function in rat models exposed to secreted tau.

Main Results:

  • A novel pathway for tau secretion and subsequent transcellular uptake was discovered.
  • Tau secreted from trisomy 21-modeling iPSCs induced synaptic impairment in rats.
  • These findings highlight the pathogenic role of extracellular tau.

Conclusions:

  • The identified tau secretion pathway offers a potential therapeutic target.
  • Extracellular tau, particularly from specific genetic backgrounds, contributes to synaptic dysfunction.
  • Further research into tau-directed therapies is warranted for neurodegenerative conditions.