Accumulating evidence suggests that tau oligomers (TauOs) prepared in vitro and derived from the brain tissue are the potent neurotoxic species causing synaptic dysfunction and impaired memory and are the seeds of intracellular tau aggregation in cellular models and in vivo [38,39,40]. Studies from human AD brains and animal models corroborate transcellular tau pathology propagation via anatomically connected brain regions, which is reminiscent of prion protein pathology [41,42]. This evidence concerns the gene MAPT and Alzheimer disease.