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.

Astrogliopathy in Tauopathies

“…In spite of the evident astrocytopathy characterized by disease-dependent stereotyped tau deposits, little is known about the functional effects of hyper-phosphorylated tau in tau-containing astrocytes in tauopathies [131]. This is due to several factors: the diversity of astrocytes, diversity of functions and gene expression profiles under various conditions and regions, as well as the lack of studies considering these variables in tauopathies.…”

Chronic traumatic encephalopathy-integration of canonical traumatic brain injury secondary injury mechanisms with tau pathology

“…Astrocytes and microglia make up two of the most important cells of the CNS innate immune system. Astrocytes containing pathologic tau have been identified in several tauopathies, including CTE (Kahlson and Colodner, 2015; McKee et al , 2016). Similarly, microglia are activated in CTE and other tauopathies (Cherry et al , 2016; Faden and Loane, 2015; Ishizawa and Dickson, 2001; Saing et al , 2012; Sasaki et al , 2008; Zilka et al , 2009a).…”

“…Under physiologic conditions astrocytes contain limited amounts of tau protein, and tau is not considered to be a major component of the astrocyte cytoskeleton (Kahlson and Colodner, 2015). However, in CTE and other tauopathies, hyperphosphorylated tau is present in astrocytes (Kahlson and Colodner, 2015; McKee et al , 2016).…”

“…However, in CTE and other tauopathies, hyperphosphorylated tau is present in astrocytes (Kahlson and Colodner, 2015; McKee et al , 2016). Although astrocytic tau pathology is not well defined in CTE, supporting neuropathological criteria for the diagnosis of CTE includes p-tau positive thorned astrocytes located at the glial limitans in the subpial and periventricular regions (McKee et al , 2016).…”

“…Although the phenotypes of the astrocytes containing hyperphosphorylated tau vary between tauopathies, thorned astrocytes, such as those characteristic of CTE, morphologically resemble reactive astrocytes and therefore may be indicative of a neuroinflammatory response similar to gliosis (Kahlson and Colodner, 2015), a process known to occur following TBI (Burda et al , 2016). The presence of hyperphosphorylated tau within astrocytes is hypothesized to have several consequences for astrocytic function (Kahlson and Colodner, 2015).…”