Glial Cells and the Propagation of Tau through the Brain in Tauopathies
Tauopathies like Alzheimer's disease are characterized by the spread of tau aggregates through the brain. Tau is one of the few molecules in the body that can become altered in a way that encourages other copies of the same molecule to also alter, causing aggregates to form. These aggregates and their surrounding biochemistry are disruptive to cell function and toxic to cells. A number of neurodegnerative conditions are associated with protein aggregates of amyloid-β, α-synuclein, and tau. The mechanisms by which this spread occurs are debated, but researchers strongly suspect a role for glial cells in this process.
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.