Abstract
Astrocytes with intracellular accumulations of misfolded phosphorylated tau protein have been observed in advanced-stage chronic traumatic encephalopathy (CTE) and in other neurodegenerative conditions. There is a growing awareness that astrocytic tau inclusions are also relatively common in the brains of persons over 70 years of age—affecting approximately one-third of autopsied individuals. The pathologic hallmarks of aging-related tau astrogliopathy (ARTAG) include phosphorylated tau protein within thorn-shaped astrocytes (TSA) in subpial, subependymal, perivascular, and white matter regions, whereas granular-fuzzy astrocytes are often seen in gray matter. CTE and ARTAG share molecular and histopathologic characteristics, suggesting that trauma-related mechanism(s) may predispose to the development of tau astrogliopathy. There are presently few experimental systems to study the pathobiology of astrocytic-tau aggregation, but human studies have made recent progress. For example, leucotomy (also referred to as lobotomy) is associated with a localized ARTAG-like neuropathology decades after the surgical brain injury, suggesting that chronic brain injury of any type may predispose to later life ARTAG. To examine this idea in a different context, we report clinical and pathologic features of two middle-aged men who came to autopsy with large (> 6 cm in greatest dimension) arachnoid cysts that had physically displaced and injured the subjects’ left temporal lobes through chronic mechanical stress. Despite the similarity of the size and location of the arachnoid cysts, these individuals had dissimilar neurologic outcomes and neuropathologic findings. We review the evidence for ARTAG in response to brain injury, and discuss how the location and molecular properties of astroglial tau inclusions might alter the physiology of resident astrocytes. These cases and literature review point toward possible mechanism(s) of tau aggregation in astrocytes in response to chronic brain trauma.
Highlights
Much remains unknown about astrocytes in healthy and diseased states
We discuss a specific subset of astrocyte pathology, related to a hypothesis that localized trauma can induce tau astrogliopathy, which is similar in appearance to age-related tau astrogliopathy (ARTAG)
It has recently become clear that chronic traumatic encephalopathy (CTE) is associated with both neuronal and glial tau pathology [1, 2]
Summary
Much remains unknown about astrocytes in healthy and diseased states. Here we discuss a specific subset of astrocyte pathology, related to a hypothesis that localized trauma can induce tau astrogliopathy, which is similar in appearance to age-related tau astrogliopathy (ARTAG).It has recently become clear that chronic traumatic encephalopathy (CTE) is associated with both neuronal and glial tau pathology [1, 2]. The CTE–NC-like changes included patchy distribution of neuronal PHF-1+ tau at sulcal depths of the cerebral cortex (Fig. 2). The distribution and proximity of the CTE–NC and ARTAG–NC to the arachnoid cysts raised the question of whether this large space-occupying lesion induced the tau proteinopathy through chronic mechanical stress.
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