TREM2 and microglia exosomes: a potential highway for pathological tau

Area of Science:

• Neuroscience
• Cell Biology
• Pathology

Background:

• Tau pathology is a hallmark of neurodegenerative diseases.
• Neuron-to-neuron transmission of tau is a key mechanism of disease progression.
• Microglia are increasingly recognized for their role in neuroinflammation and disease spread.

Discussion:

• This commentary discusses a study investigating the role of TREM2 (T-cell immunoglobulin and mucin domain-containing protein 3) in tau pathology.
• The study found that TREM2 deficiency led to increased tau pathology spread.
• This exacerbation was linked to microglial exosomes, suggesting a novel transmission route.

Key Insights:

• Loss of TREM2 expression significantly worsens tau pathology spread.
• Microglial exosomes are implicated as mediators in the intercellular transmission of tau.
• The microglial endolysosomal system is crucial for regulating tau propagation.

Outlook:

• Further research into TREM2 and microglial exosomes could reveal new therapeutic targets for tauopathies.
• Understanding these mechanisms is vital for developing strategies to halt or slow neurodegenerative disease progression.
• This work underscores the complex interplay between glial cells and proteinopathies.