MAPT and tauopathy: Although the tau aggregation pathway, as well as its filament structure and composition, are not universal but specific to each tauopathy, in general, it involves the following steps: (1) acquiring aggregation-competent conformation that differs from the paperclip-like conformation of physiological tau in solution; (2) formation of dimers and small soluble oligomers (pre-tangles); and (3) formation of filamentous inclusions (Sanders et al., 2014; Falcon et al., 2018, 2019; Cieplak, 2019).