The pathological propagation of Tau protein is a hallmark of multiple neurodegenerative disorders, collectively referred to tauopathies with Alzheimer's disease (AD) being most prevalent, but including a range of frontotemporal dementias (FTDs). The extracellular Tau is important during the progression of tauopathies, although Tau is mainly expressed intracellularly for physiological functions. Extracellular Tau could be actively secreted by one cell then taken up by adjacent cells, leading to the cell-to-cell transmission of Tau. Accumulating evidence has demonstrated that Tau propagation is not only by the trans-synaptic spreading but also via exo-synaptic spreading pathways especially under the pathological conditions. Among these, exosomes, microvesicles and tunneling nanotubes (TNTs) are proposed exo-synaptic pathways for the spread of Tau pathology. These findings have led to the idea that extracellular Tau could be a novel therapeutic target to halt the propagation of Tau pathology. From this perspective, this charter focuses on recent advances in understanding the mechanisms of Tau secretion and discusses the role of such mechanisms in the development of Tau pathology.
Keywords: Alzheimer’s disease; Exosomes; Microvesicles; Tauopathies; Tunneling nanotubes.