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Discovery and engineering of an anti-TREM2 antibody to promote amyloid plaque clearance by microglia in 5XFAD mice
Development of an antibody to help brain immune cells clear amyloid plaques in Alzheimer's model mice
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Abstract
Ab2 TVD-Ig treatment increased microglial phagocytosis of amyloid plaques by more than 100-fold.
- Engineering a bispecific antibody enhanced its ability to activate TREM2 and penetrate the brain.
- The tetra-variable domain immunoglobulin (TVD-Ig) form significantly improved the microglial response to amyloid-β oligomers.
- Microglia migration and survival were elevated by 100-fold with the use of the Ab2 TVD-Ig compared to bivalent IgG.
- The bispecific antibody targeting the transferrin receptor achieved a 10-fold increase in brain antibody concentration.
- Treatment of 5-month-old with the Ab2 TVD-Ig/αTfR antibody significantly enhanced interactions between microglia and amyloid plaques.
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Key numbers
100-fold
Increase in Phagocytosis
Improvement in microglial phagocytosis of amyloid plaques with Ab2 TVD-Ig vs. bivalent IgG.
10-fold
Brain Concentration Increase
Increase in brain antibody concentration with Ab2 TVD-Ig/αTfR bispecific antibody.
7×
Microglia Clustering Increase
IBA1 area increase in treated with Ab2 TVD-Ig/αTfR.