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Efficient Mammalian Cell Expression and Single-step Purification of Extracellular Glycoproteins for Crystallization
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The Jekyll and Hyde of TREM2

Javier Rueda-Carrasco1, Soyon Hong1

  • 1UK Dementia Research Institute at University College London, Institute of Neurology, Gower Street, London WC1E 6BT, UK.

Trends in Neurosciences
|September 1, 2020
PubMed

Insights

The TREM2R47H variant may protect against tau neurodegeneration, suggesting its role depends on the specific Alzheimer

Area of Science:

  • Neuroscience
  • Genetics
  • Alzheimer's Disease Research

Background:

  • Alzheimer's disease (AD) involves complex pathologies, including amyloid-beta (Aβ) plaques and tau tangles.
  • The TREM2 gene, particularly the R47H variant, is a significant genetic risk factor for late-onset AD.
  • Microglia, the brain's immune cells, play a crucial role in AD pathogenesis, with TREM2 signaling influencing their function.

Purpose of the Study:

  • To investigate the specific role of the TREM2R47H variant in tau-mediated neurodegeneration.
  • To explore the context-dependent functions of TREM2 in different Alzheimer's disease pathologies (Aβ vs. tau).

Main Methods:

  • Utilized a mouse model of tauopathy to study tau-mediated neurodegeneration.
  • Assessed the impact of the TREM2R47H variant on microglial responses and neuroinflammation in the context of tau pathology.

Main Results:

  • Demonstrated a potential neuroprotective effect of the TREM2R47H variant against tau-mediated neurodegeneration.
  • Highlighted that microglial responses to TREM2 signaling are context-dependent, differing between Aβ and tau pathologies.
  • Suggests TREM2 may have opposing roles in Aβ-driven versus tau-driven Alzheimer's disease processes.

Conclusions:

  • The TREM2R47H variant may confer protection against tau pathology, contrary to its established risk association with overall AD.
  • Microglial function, modulated by TREM2, exhibits distinct behaviors in response to different AD pathological hallmarks.
  • TREM2's role in Alzheimer's disease appears to be dichotomous, potentially acting antagonistically in Aβ and tau pathways.
Keywords:
Alzheimer’s diseaseTREM2microgliatauopathy

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