The potential role of glial cells in driving the prion-like transcellular propagation of tau in tauopathies

• Main Authors: Zein Amro, Andrea J. Yool, Lyndsey E. Collins-Praino
• Format: Article
• Language: English
• Published: Elsevier 2021-07-01
• Series: Brain, Behavior, & Immunity - Health
• Subjects: Alzheimer’s disease; Prion-like hypothesis; Astrocytes; Microglia; Neuroinflammation
• Online Access: http://www.sciencedirect.com/science/article/pii/S2666354621000454

Dementia is one of the leading causes of death worldwide, with tauopathies, a class of diseases defined by pathology associated with the microtubule-enriched protein, tau, as the major contributor. Although tauopathies, such as Alzheimer’s disease and Frontotemporal dementia, are common amongst the ageing population, current effective treatment options are scarce, primarily due to the incomplete understanding of disease pathogenesis. The mechanisms via which aggregated forms of tau are able to propagate from one anatomical area to another to cause disease spread and progression is yet unknown. The prion-like hypothesis of tau propagation proposes that tau can propagate along neighbouring anatomical areas in a similar manner to prion proteins in prion diseases, such as Creutzfeldt-Jacob disease. This hypothesis has been supported by a plethora of studies that note the ability of tau to be actively secreted by neurons, propagated and internalised by neighbouring neuronal cells, causing disease spread. Surfacing research suggests a role of reactive astrocytes and microglia in early pre-clinical stages of tauopathy through their inflammatory actions. Furthermore, both glial types are able to internalise and secrete tau from the extracellular space, suggesting a potential role in tau propagation; although understanding the physiological mechanisms by which this can occur remains poorly understood. This review will discuss the current literature around the prion-like propagation of tau, with particular emphasis on glial-mediated neuroinflammation and the contribution it may play in this propagation process.