We anticipate that differences between tau conformers in their endogenous ability to regulate kinesin, in addition to disparities in aggregation and fragmentation rates (among others), is a parsimonious mechanism that, coupled with networked, trans-synaptic spread, drives not only heterogeneity within a given tauopathy but also the distinct pathophysiologies of different tauopathies. This evidence concerns the gene MAPT and tauopathy.