Prospect of therapeutic approaches to tauopathies

Alois Alzheimer described the concurrence of two conspicuous proteinacious aggregates in 1906. Today it is clear that the two types of protein aggregates are fundamentally different. One consists of a short fragment (Aβ peptide) of a membrane protein APP and is found mainly outside of cells and the other is formed from a biochemically modified cytoskeleton-associated protein known as tau. The latter is found exclusively inside cells. Aggregated tau in all tauopathies including AD is abnormally modified by the excess incorporation of chemical groups called phosphates (hyperphosphorylation), and the appearance of this biochemical change coincides with the onset all tauopathies, suggesting that it is both a necessary and sufficient cause for such diseases. Data indicate that the basis for tau hyperphosphorylation is the dysregulation of key enzymes known as kinases. These enzymes are therapeutic targets for AD and other neurodegenerative diseases, which feature pathological tau structures in brain