MAPT and Alzheimer disease: To look more broadly at tau conformers in DS and AD, we performed sarkosyl extraction of insoluble tau from fresh-frozen frontal cortex samples (Supplementary Table S2) and used a HTRF assay to measure aggregated tau species (Supplementary Fig. S2A, B) to select a subset of well-matched samples for Western blot (Supplementary Fig. S2C–F).