Taken together, these in vivo findings indicate for the first time that tau-directed immunotherapy offers strong protection against cognitive dysfunction, oxidative stress, neurochemical and histological alterations occurring in STZ-induced mouse model of AD, which highlights the potential of non-invasive administration of 12A12mAb in the treatment of both familial and sporadic form of this age-related progressive neurodegenerative disorder. This evidence concerns the gene MAPT and Alzheimer disease.