Remarkably, the cleavage-specific 12A12mAb—which selectively binds 20–22 kDa NH2htau without unproductive and deleterious cross-reaction towards the physiological intact tau—appears to be potent tool by providing measurable changes on Alzheimer’s disease brain physiopathology which result in significant improvement of the synaptic and cognitive deficits in affected animals, even after its short-term (14 days) i.v. delivery. This evidence concerns the gene MAPT and Cognitive impairment.