TREM2 (Triggering Receptor Expressed on Myeloid Cells 2) is a transmembrane receptor primarily expressed on microglia, the resident immune cells of the central nervous system. It plays a critical role in modulating microglial functions, including phagocytosis, inflammation regulation, and cellular survival. Genetic variants of TREM2. such as R47H, are strongly linked to an increased risk of neurodegenerative diseases, particularly Alzheimer’s disease (AD), highlighting its importance in brain homeostasis and disease pathology.
TREM2 antibodies are tools designed to target and modulate TREM2 activity, either by activating or inhibiting its signaling. Agonistic antibodies enhance TREM2-mediated microglial responses, promoting clearance of toxic protein aggregates like amyloid-beta plaques in AD models. Antagonistic antibodies, conversely, aim to suppress excessive neuroinflammation associated with TREM2 dysfunction. These antibodies are also used as research reagents to study TREM2 expression, trafficking, and interactions with ligands like APOE and phospholipids.
Therapeutic development faces challenges, including blood-brain barrier penetration and ensuring cell-specific targeting. Nonetheless, TREM2 antibodies hold promise for treating AD, Parkinson’s disease, and ALS. Clinical trials, such as those evaluating AL002 (an anti-TREM2 antibody), aim to validate their efficacy in slowing neurodegeneration. Beyond therapy, TREM2 antibodies serve as biomarkers to monitor disease progression or microglial activation states in neurological disorders.