Figure 2.

Therapeutic strategies for prevention of tau pathology in tauopathies. Illustration of the spatiotemporal pattern of the propagation of tau pathology in Alzheimer's disease (AD) and Progressive supranuclear palsy (PSP). Six stages (I–VI) of tau pathology can be observed in both diseases (top blue arrow). The affected regions in the brain are indicated by spiky circles. Tau pathology begins in distinct regions in each of these tauopathies and propagates differently. Tau pathology is predominant in neurons in AD brain while neurons and glial cells are affected in PSP. Different toxic forms of tau are observed during the course of the disease. They present a low toxicity (pink in AD and yellow in PSP) at early stages of the disease and high toxicity (dark red in AD and brown in PSP) at late stages of the disease. These forms are distinct in AD (yellow to brown) and PSP (pink to dark red). A therapeutic molecule should be designed for each toxic form of tau (yellow, brown, pink, and dark red dots). The therapeutic strategy should also be adapted to the stages of disease as tau forms vary during the course of the disease. Because the toxic forms of tau differs in AD and PSP, a molecule not specific to these forms (blue dot, common treatment) might be inefficient and even detrimental to patients by affecting forms of tau that are not toxic.