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Tau and neurodegeneration.

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Tau protein tangles are linked to Alzheimer's disease and other neurodegenerative conditions. Recent research reveals how tau filaments spread through the brain, aiding in disease classification and understanding.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Tau protein, identified in 1975, was linked to Alzheimer's disease in 1985.
  • Hyperphosphorylated tau forms filamentous inclusions in neurodegenerative diseases, including frontotemporal dementia caused by MAPT gene mutations.
  • Most tauopathies are sporadic, but tau filament assembly can drive neurodegeneration and dementia.

Purpose of the Study:

  • To summarize the historical understanding and recent advancements in tau research.
  • To highlight the role of tau pathology in neurodegenerative diseases.
  • To explain the prion-like spread of tau pathology and its implications for disease classification.

Main Methods:

  • Historical literature review.
  • Analysis of genetic studies identifying MAPT mutations.
  • Review of experimental systems demonstrating tau spread.
  • Examination of high-resolution structural studies on human brain tauopathies.

Main Results:

  • Tau pathology is central to Alzheimer's disease and other tauopathies.
  • Mutations in the MAPT gene cause inherited frontotemporal dementia with tau inclusions.
  • Filamentous tau assemblies can propagate in a prion-like manner across brain regions.
  • Structure-based classification of tauopathies has advanced understanding of filament formation.

Conclusions:

  • Aberrant tau assembly is sufficient to cause neurodegeneration and dementia.
  • Understanding tau filament formation and spread is crucial for classifying and potentially treating tauopathies.
  • Recent structural studies offer new insights into the mechanisms of tauopathies.