MAPT and Alzheimer disease: In particular, while the secretion (103–105) and uptake (92) of tau itself in cellular models has been demonstrated and linked to the elevated tau levels in early AD (106), it is unclear how secretion is related to the spreading of neurofibrillary lesions and whether that occurs via an oligomer-associated mechanism, such as templated misfolding or ionophore formation (107, 108), or via some mechanism that does not require the tau MTBR at all (109–112).