Is tau a prion-like protein?

It has been over a quarter century since the discovery in the mid-1980s that the paired helical filaments of neurofibrillary tangles were made up of abnormally hyperphosphorylated tau. A decade earlier tau had been first isolated from porcine brain as a heat stable protein essential for microtubule assembly. The following years clearly established tau as a microtubule-associated protein that under physiological conditions regulates microtubule assembly, dynamic behavior, and spatial organization, and has also been shown to regulate the axonal transport of organelles, including mitochondria. Further studies during the following couple of decades revealed the importance of post-translational modifications, mainly phosphorylation but also truncation, in tau function and dysfunction. Prominent tau pathology is present in a number of neurodegenerative disorders, predominantly within the neuronal compartment, but also within glial cells. Because of this shared histopathological feature, they are referred collectively as tauopathies, although they constitute a group of etiologically heterogeneous, clinically, and neuropathologically overlapping disease entities. In tauopathies, the intracellular soluble tau forms filamentous structures of aggregated, hyperphosphorylated tau, which are associated with synaptic loss and neuronal death. The occurrence of fibrillar tau inclusions in tauopathies strongly supports a key role in the observed clinical symptoms and pathology but the