Activation of TREM2 via single-domain antibodies improves synaptic and cognitive function in 5×FAD mice.

Activation of TREM2 with single-domain antibodies 10C11 and 10E12 improves cognition and reduces pathology in 5×FAD mice, with 10E12 decreasing Aβ plaques by targeting microglia.

• Why it matters: Understanding how TREM2 activation benefits Alzheimer’s disease is crucial because microglial dysfunction increases disease risk, and current therapies lack clarity on underlying mechanisms.
• What they did: Researchers developed two TREM2-activating single-domain antibodies and injected them into the ventral hippocampus of early-stage 5×FAD mice, assessing their effects on microglia, plaques, and synapses.
• The result: Both antibodies enhanced microglial activity and rescued cognitive deficits; 10E12 lowered Aβ plaques and preserved synaptic function, while 10C11 protected synapses without reducing plaques, highlighting multifaceted therapeutic mechanisms.