Herein, we developed a panel of agonistic and antagonistic mAbs, binding the extracellular domain of TREM2 the selected antibody of which was shown to be capable of activating microglia expressing TREM2 thereby facilitating uptake of oligomeric beta amyloid and attenuating cognitive decline in amyloidopathy models of Alzheimer’s disease but would also be relevant to all neurodegenerative diseases. This evidence concerns the gene TREM2 and early-onset autosomal dominant Alzheimer disease.