MAPT and Alzheimer disease: ER responds to (a) increased ROS, protein production/availability (e.g., due to tau hyperphosphorylation), or to (b) mutant (mutant PS2 or tau overexpression), unfolded or misfolded proteins (e.g., oxidised Aβ, AβO and S-nitrosylation of molecular chaperons, MITO proteins, and synapse proteins in AD) with activation of the unfolded protein response (UPR).