FIGURE 2.

Neuron-to-neuron transfer of tau. The processes involved in tau propagation can be divided into three basic steps: (1) the pathological form of tau is released into the extracellular space from the donor cell; (2) the pathological tau released into the extracellular space is taken up by recipient cells; and (3) the pathological tau taken up into the recipient cells forms new intracellular aggregates. Tau exists in various forms in terms of biochemical property, including monomeric, oligomeric, truncated, and phosphorylated forms. Additionally, tau may undergo a wide range of posttranslational modifications, including acetylation, glycation, isomerization, nitration, SUMOylation, and ubiquitination or a mixture of these modifications. It is still largely unknown which forms of tau are released into the extracellular space and involved in tau propagation.