Compounds that alter neuronal tau aggregate formation could act by one of several mechanisms, including modulation of (1) exogenous AD-tau internalization; (2) intracellular trafficking of AD-tau after internalization; (3) tau fibril elongation; (4) tau fibril degradation; or (5) tau protein expression at the transcriptional or post-transcriptional levels. This evidence concerns the gene MAPT and Alzheimer disease.