TREM2, microglia, and Alzheimer's disease

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Genome-wide association studies (GWAS) link Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) to Alzheimer's disease (AD) pathogenesis.
• Increasing research focuses on TREM2's specific roles in AD pathology.

Purpose of the Study:

• To review TREM2 biology and its functions in microglia within the context of AD.
• To elucidate the multiple mechanisms of TREM2 in AD pathogenesis.
• To identify key questions for future research on TREM2's role in microglial responses.

Main Methods:

• Literature review and synthesis of current research on TREM2.
• Analysis of TREM2's involvement in microglial functions.
• Exploration of TREM2's interactions with AD pathologies and other molecules like APOE.

Main Results:

• TREM2 is hypothesized to be a multifaceted regulator of microglial functions essential for AD brain homeostasis.
• TREM2 influences microglial roles in amyloid and tau pathologies.
• TREM2 modulates inflammatory responses and cellular metabolism in AD, potentially interacting with APOE.

Conclusions:

• TREM2 plays a broad and critical role in microglial function relevant to Alzheimer's disease.
• Understanding TREM2's mechanisms offers potential for novel immunomodulatory therapeutic strategies for AD.
• TREM2's involvement spans amyloid/tau pathologies, inflammation, and metabolism, highlighting its complex role.