MAPT and Alzheimer disease: This heterodimer is linked to up to 50% of gene expression changes in AD brain, and its induction in neurons is sufficient to elicit AD-typical neuronal changes, including the hyperphosphorylation and secretion of tau, increased Aβ42 over Aβ40 production, and disrupted expression of components of the retromer [6], which functions in endosomal-lysosomal trafficking and is defective in AD brain [8, 9].