Taken together, these results indicate that 12A12mAb-mediated neutralization of the neurotoxic NH2htau exerts in vivo, in hippocampus and retina from Tg2576 AD mice, an anti-amyloidogenic action involving, respectively, the upregulation in the synaptic expression of neuron-specific BIN1 alone or together with RIN3, two key endocytic adaptors governing in opposite ways the dynamic convergence of APP and BACE1 into Rab5-positive endosome and then the Aβ generation. Here, BACE1 is linked to Alzheimer disease.