**2. Tau biology and pathology**

Tau pathology, namely fibrillary tangles, was observed way before the protein was identified. In fact, it was Alois Alzheimer who first described the heavy burdens of this never reported feature in his demented patient back to 1906 [6]. Seventy years later, tau protein was isolated as a factor that is critical for the re-polymerization of some depolymerized tubulins to form microtubules in vitro [7]. After another 10 years, a series studies confirmed that the tangles observed in AD brain are composed of tau [3, 8–10]. Since then, tau received significant attention in AD research. Nevertheless, as researchers soon realized tau pathology in a panel of neurological dysfunction, solving the underlying mechanism of tauopathy has been regarded as a unique field of neurobiology.
