MAPT and Alzheimer disease: By combining Kopke’s and Guo’s protocols [28, 39], we separated various tau fractions from AD brains, oligomeric fraction (O-tau), and sarkosyl-insoluble fractions 1 and 2 (SI1-tau and SI2-tau), and heat-stable tau (HS-tau) (Fig. 1), by sedimentation in sarkosyl buffer and assessed their seeding activity by using new methods we recently developed [26].