TREM2 in Neurodegenerative Diseases.

Area of Science:

• Neuroimmunology
• Neurodegenerative Diseases
• Molecular Biology

Background:

• TREM2 variants are significant risk factors for Alzheimer's disease (AD) and other neurodegenerative diseases (NDDs).
• TREM2, expressed on immune cells, highlights the immune system's active role in NDD pathogenesis.
• TREM2 variants represent the highest AD risk factor identified in two decades, underscoring the need for functional understanding.

Purpose of the Study:

• To comprehensively review current understanding of TREM2 biology in NDDs.
• To clarify TREM2's expression, signaling, and function in the context of neuroinflammation.
• To explore potential applications of TREM2 research for NDD biomarkers and therapeutics.

Main Methods:

• Literature review of TREM2 expression, signaling, and function in NDDs.
• Analysis of in vitro and in vivo studies on TREM2 regulation by inflammatory stimuli.
• Synthesis of findings regarding TREM2's dual role in inflammation.

Main Results:

• In vivo inflammatory stimuli consistently increase TREM2 expression, contrary to some in vitro findings.
• TREM2 exhibits a complex, often pro-inflammatory role, challenging its classical anti-inflammatory description.
• Current literature clarifies several aspects of TREM2 biology, though open questions remain.

Conclusions:

• TREM2's intricate immune functions are critical in NDD pathogenesis.
• Understanding TREM2's complex inflammatory role is essential for developing targeted NDD therapies.
• TREM2 biology offers promising avenues for novel immune-directed biomarkers and therapeutics for NDDs.