Although the protofibril structures from 3R−/4R-tauopathies (AD and CTE) and a 3R-tauopathy (PiD) were resolved by cryo electron microscopy (Cryo-EM) [23, 25, 26], it had previously been a challenge to isolate sufficient sarkosyl-insoluble fibrillar tau from 4R-tauopathies (e.g. PSP, CBD and argyrophilic grain disease). This evidence concerns the gene MAPT and Alzheimer disease.