학술논문

Detection of astrocytic tau pathology facilitates recognition of chronic traumatic encephalopathy neuropathologic change
Document Type
article
Source
Acta Neuropathologica Communications. 10(1)
Subject
Biochemistry and Cell Biology
Biological Sciences
Neurosciences
Traumatic Brain Injury (TBI)
Physical Injury - Accidents and Adverse Effects
Traumatic Head and Spine Injury
Brain Disorders
Dementia
Neurodegenerative
Acquired Cognitive Impairment
Neurological
Alzheimer Disease
Astrocytes
Brain
Brain Injuries
Traumatic
Chronic Traumatic Encephalopathy
Humans
Neuropathology
tau Proteins
CONNECT-TBI Investigators
Aging-related tau astrogliopathy
Chronic traumatic encephalopathy
Neurodegeneration
Tau
Traumatic brain injury
Clinical Sciences
Biochemistry and cell biology
Language
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.