Glial Tau Pathology in Tauopathies: Functional Consequences

Abstract

Tauopathies are a class of neurodegenerative diseases characterized by the presence of hyperphosphorylated and aggregated tau pathology in neuronal and glial cells. Though the ratio of neuronal and glial tau aggregates varies across diseases, glial tau aggregates can populate the same degenerating brain regions as neuronal tau aggregates. While much is known about the deleterious consequences of tau pathology in neurons, the relative contribution of glial tau pathology to these diseases is less clear. Recent studies using a number of model systems implicate glial tau pathology in contributing to tauopathy pathogenesis. This review aims to highlight the functional consequences of tau overexpression in glial cells and explore the potential contribution of glial tau pathology in the pathogenesis of neurodegenerative tauopathies.

Keywords: astrocytes; functional consequences; glial tau pathology; microglia; neurodegeneration; oligodendrocytes; tau; tauopathy.

Figure 1

Schematic of functional consequences associated with tau pathology in glial cells. Tau overexpression disrupts oligodendrocyte (blue) and astrocyte (green) physiology and has been shown to lead to deficits in (A) myelin sheath integrity, (B) glutamate buffering at the synapse, and (C) maintenance of the BBB. These consequences are associated with neuronal degenerative changes and neuronal death. (D) Microglial cells (purple) have been shown to contribute to the spread of tau pathology across brain regions.