Untangling the tauopathies: Current concepts of tau pathology and neurodegeneration.

Tau is the most common misfolded protein responsible for human neurodegenerative diseases. The identification of mutations in MAPT, the gene that encodes tau, causing dementia and parkinsonism established the notion that tau aggregation is responsible for the development of disease. An increased understanding of the pathway leading from conformational changes in tau protein and tau propagation to neuronal dysfunction, cell death and clinical manifestation will be the key for the development mechanism-based therapeutic strategies for tauopathies.