The propagation mechanisms of extracellular tau in Alzheimer’s disease

Tubulin-associated unit (tau) is an important microtubule-associated protein. The abnormal intracellular aggregation of tau has been strongly associated with Alzheimer's disease (AD). Accumulating evidence has conclusively demonstrated that tau is present in the cytoplasm of neurons and is also actively released into the extracellular space. However, the types of tau species that are released are unclear, as is the mechanism of their release by donor neurons and subsequent uptake by recipient neurons in AD. Understanding the underlying mechanisms of abnormal tau cell-to-cell transmission can provide novel insights into the etiology and pathogenesis of AD and can help identify new targets for the development of AD therapies focused on counteracting neurodegeneration or even preventing it. From this perspective, the present review focuses on recent advances in understanding the mechanisms regulating the levels of extracellular tau and discusses the role of such mechanisms in the propagation of tau-associated pathology.