Altered oligodendroglia and astroglia in chronic traumatic encephalopathy

Abstract

Chronic traumatic encephalopathy (CTE) is a progressive tauopathy found in contact sport athletes, military veterans, and others exposed to repetitive head injury (McKee et al. 2009(McKee et al. , 2013(McKee et al. , 2016Omalu et al. 2005Omalu et al. , 2006Martland 1928;Critchley 1949). White matter atrophy and axonal loss have been reported in CTE but have not been characterized on a molecular or cellular level (McKee et al. 2013;Holleran et al. 2017;Hsu et al. 2018). Here, we report 24,735 single nucleus RNA-seq profiles from dorsolateral frontal white matter cell nuclei from eight individuals with neuropathologically confirmed CTE and eight age-and sex-matched controls. We identified eighteen transcriptionally distinct nuclei clusters, as well as cell-type-specific differences between conditions. The findings support a global loss of oligodendrocytes (OLs) in CTE, alterations in OL subpopulations, and suggest pathological iron accumulation in OL subpopulations. Total astrocyte number was not different between CTE and controls but showed upregulation of transcripts associated with neuroinflammation. These findings provide novel insight into the molecular and cellular underpinnings of white matter atrophy in CTE, which may lead to an improved understanding of the disease pathogenesis.

Aging-Related Tau Astrogliopathy in Aging and Neurodegeneration

“…Over the last 20 years, our focus on astrocytic dysfunction and pathology has enabled significant progress in an area of research that holds great promise for the treatment of a number of brain disorders. The identification of ARTAG in 2016 [ 2 ] marks a significant milestone in this journey and there is now good conceptual evidence for a link between ARTAG pathology, particularly GFAs, as a precursor to FTLD-tau and accumulating evidence of the importance of TSAs in the pathogenesis of CTE [ 88 , 102 , 103 ]. Whilst encouraging, there are still many knowledge gaps and further research is required to answer a number of fundamental questions pertaining to the etiology of ARTAG, its clinical significance and its role in neurodegeneration.…”