MAPT and Alzheimer disease: The prion-like strain effects of misfolded tau conformers lead to a series of critical mechanistic questions relating to the role of misfolded tau aggregates in distinct phenotypes of AD and FTLD: (i) What is the molecular mechanism of replication and propagation of distinct brain-derived pathogenic aggregates, particularly prefibrillar forms of tau, in different phenotypes of AD and FTLD-tau?