TREM2 is a receptor found on microglia in the brain, and in recent years researchers have found that targeting it with antibodies can enhance clearance of amyloid-β in mouse models of Alzheimer's disease. The microglia, responsible for clearing molecular waste, are stimulated to greater activity by this interaction with TREM2. The usual caveats apply here, such as the artificiality of mouse models for this condition, and the fact that successful clearance of amyloid-β via immunotherapy in Alzheimer's patients has not resulted in meaningful improvement to symptoms. Nonetheless, work on amyloid-β clearance continues, with the hope that early intervention, in the years prior to the point at which Alzheimer's manifests, during which amyloid-β levels slowly increase in the brain, will push back onset of the condition.
A newly developed agonistic antibody reduced the amyloid pathology in mice with Alzheimer's disease, signaling its promise as a potential treatment for the disease. Researchers found that a tetra-variable domain antibody targeting the triggering receptor expressed on myeloid 2 (TREM2) - dubbed TREM2 TVD-lg - reduced amyloid burden, eased neuron damage, and alleviated cognitive decline in mice with Alzheimer's disease.
TREM2 is a single-pass receptor expressed by microglia - supportive cells that function as scavengers in the central nervous system. The antibody increased TREM2 activation and promoted phagocytosis of amyloid and microglia survival. Microglia play a crucial role in the removal of amyloids that cluster around amyloid-beta plaques, a hallmark of Alzheimer's disease. While previous research has shown that TREM2 plays an important role in the pathophysiology of Alzheimer's disease, the recent findings suggest that increasing TREM2 activation could have therapeutic effects such as improved cognition.