MAPT and Alzheimer disease: To assess the bioactivity of the AD-tau, we adopted a previously reported neuron culture-based assay [14] that can sensitively differentiate tau pathology induced by different human-derived tau strains, including AD, CBD, and PSP tau strains, and does not respond to heparin-induced tau pffs (hep-pffs), ensuring that any observed pathology is the consequence of the added human pathogenic tau material [31].