MAPT and Alzheimer disease: Exposure of RA-differentiated SH-SY5Y cells to misfolded AD brain-derived tau proteins at day 4 (Fig 4A) induced progressive accumulation of triton-insoluble aggregates of tau proteins in a concentration-dependent manner (Fig 4C, 4D, and 4E) with no apparent direct cytotoxicity as indicated by no significant change in levels of lactate dehydrogenase (LDH) leakage into media (Fig 4B).