Figure 1

Potential therapeutic targets to slow or prevent the spread of tau pathology in the brain. The mechanisms by which toxic tau species are transferred between cells are not known; further investigation is required to understand how tau is released into extracellular space and internalized. It is also unclear which species of tau are involved at each stage; neurons may release monomeric or oligomeric tau, which may include toxic forms of soluble tau. Released tau may also be misfolded, and may have modifications such as abnormal phosphorylation, truncation or both. As these mechanisms are better understood, potential therapeutic targets that will prevent or slow the spread of pathological tau may be uncovered. For example, the release and uptake of tau may be inhibited pharmacologically, and immunotherapy might lower extracellular tau concentration. Furthermore, anti-aggregant drugs may prevent tau oligomerization, reducing levels of potentially toxic forms of tau that are available to be internalized.