MAPT and Alzheimer disease: Ultimately, numerous hypotheses based on diverse lines of investigation converge on the concept that the accumulation of the Aβ and tau aggregates that characterize AD, aging, cognitive impairment, and other neurodegenerative conditions result from impairment in the clearance of these macromolecules from the brain and that dysfunctions in clearance may, in part, be attributable to lymphatic dysfunction.