Overall, our in vivo observations further support the conclusion that: (i) the elevation of Arc/Arg3.1 is connected with functional visual impairments and not a mere consequence of tau pathology; and (ii) the most toxic soluble species, including the truncated ones (i.e., NH2htau), but not the neurofibrillary aggregates are per se responsible for the general progressive deterioration of the functional network connectivity during the AD development and that their deleterious effects are reversible in vivo. The gene discussed is MAPT; the disease is Alzheimer disease.