Detection of astrocytic tau pathology facilitates recognition of chronic traumatic encephalopathy neuropathologic change

Acta Neuropathologica Communications

CONNECT-TBI Investigators¹  Douglas H. Smith²  Abigail Bretzin³  Douglas J. Wiebe³  Daniel P. Perl⁴  David S. Priemer⁴  Diego Iacono⁴  Lili-Naz Hazrati⁵  C. Dirk Keene⁶  Amber Nolan⁶  Edward B. Lee⁷  Julia Kofler⁸  Kamar E. Ameen-Ali⁹  William Stewart⁹  Rebecca Folkerth^1,10  Gabor G. Kovacs^1,11 

[1] ;Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania;Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania;Department of Defense/Uniformed Services, University Brain Tissue Repository and Neuropathology Program, Uniformed Services University;Department of Laboratory Medicine and Pathobiology, University of Toronto;Department of Laboratory Medicine and Pathology, University of Washington;Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania;Department of Pathology, University of Pittsburgh School of Medicine;Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital;Office of Chief Medical Examiner;Tanz Centre for Research in Neurodegenerative Disease (CRND) and Department of Laboratory Medicine and Pathobiology, Krembil Discovery Tower, University of Toronto;

关键词: Chronic traumatic encephalopathy;    Traumatic brain injury;    Neurodegeneration;    Tau;    Aging-related tau astrogliopathy;   

DOI  :  10.1186/s40478-022-01353-4

来源: DOAJ

【 摘 要 】

Abstract Traumatic brain injury (TBI) is associated with the development of a range of neurodegenerative pathologies, including chronic traumatic encephalopathy (CTE). Current consensus diagnostic criteria define the pathognomonic cortical lesion of CTE neuropathologic change (CTE-NC) as a patchy deposition of hyperphosphorylated tau in neurons, with or without glial tau in thorn-shaped astrocytes, typically towards the depths of sulci and clustered around small blood vessels. Nevertheless, although incorporated into consensus diagnostic criteria, the contribution of the individual cellular components to identification of CTE-NC has not been formally evaluated. To address this, from the Glasgow TBI Archive, cortical tissue blocks were selected from consecutive brain donations from contact sports athletes in which there was known to be either CTE-NC (n = 12) or Alzheimer’s disease neuropathologic change  (n = 4). From these tissue blocks, adjacent tissue sections were stained for tau antibodies selected to reveal either solely neuronal pathology (3R tau; GT-38) or mixed neuronal and astroglial pathologies (4R tau; PHF-1). These stained sections were then randomised and independently assessed by a panel of expert neuropathologists, blind to patient clinical history and primary antibody applied to each section, who were asked to record whether CTE-NC was present. Results demonstrate that, in sections stained for either 4R tau or PHF-1, consensus recognition of CTE-NC was high. In contrast, recognition of CTE-NC in sections stained for 3R tau or GT-38 was poor; in the former no better than chance. Our observations demonstrate that the presence of both neuronal and astroglial tau pathologies facilitates detection of CTE-NC, with its detection less consistent when neuronal tau pathology alone is visible. The combination of both glial and neuronal pathologies, therefore, may be required for detection of CTE-NC.

【 授权许可】

Unknown