Abstract
Chronic traumatic encephalopathy (CTE) is a neurodegeneration characterized by the abnormal accumulation of hyperphosphorylated tau protein within the brain. Like many other neurodegenerative conditions, at present, CTE can only be definitively diagnosed by post-mortem examination of brain tissue. As the first part of a series of consensus panels funded by the NINDS/NIBIB to define the neuropathological criteria for CTE, preliminary neuropathological criteria were used by 7 neuropathologists to blindly evaluate 25 cases of various tauopathies, including CTE, Alzheimer’s disease, progressive supranuclear palsy, argyrophilic grain disease, corticobasal degeneration, primary age-related tauopathy, and parkinsonism dementia complex of Guam. The results demonstrated that there was good agreement among the neuropathologists who reviewed the cases (Cohen’s kappa, 0.67) and even better agreement between reviewers and the diagnosis of CTE (Cohen’s kappa, 0.78). Based on these results, the panel defined the pathognomonic lesion of CTE as an accumulation of abnormal hyperphosphorylated tau (p-tau) in neurons and astroglia distributed around small blood vessels at the depths of cortical sulci and in an irregular pattern. The group also defined supportive but non-specific p-tau-immunoreactive features of CTE as: pretangles and NFTs affecting superficial layers (layers II–III) of cerebral cortex; pretangles, NFTs or extracellular tangles in CA2 and pretangles and proximal dendritic swellings in CA4 of the hippocampus; neuronal and astrocytic aggregates in subcortical nuclei; thorn-shaped astrocytes at the glial limitans of the subpial and periventricular regions; and large grain-like and dot-like structures. Supportive non-p-tau pathologies include TDP-43 immunoreactive neuronal cytoplasmic inclusions and dot-like structures in the hippocampus, anteromedial temporal cortex and amygdala. The panel also recommended a minimum blocking and staining scheme for pathological evaluation and made recommendations for future study. This study provides the first step towards the development of validated neuropathological criteria for CTE and will pave the way towards future clinical and mechanistic studies.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-015-1515-z) contains supplementary material, which is available to authorized users.
Highlights
In 1928, the pathologist and medical examiner, Harrison Stanford Martland, introduced the term ‘punch-drunk’ to describe the clinical features of a distinct neuropsychiatric syndrome that affected boxers [26]; a condition that later came to be known as ‘dementia pugilistica’ [33]
In the 15 other tauopathy cases (Supplementary Table 2), the reviewers generally agreed with the submission diagnoses of Alzheimer’s disease (AD) (97.1 % of responses), corticobasal degeneration (CBD) (92.8 %), and PART (78.5 %); there were frequent discrepancies in cases with the presumptive diagnoses of progressive supranuclear palsy (PSP), AGD and Guamanian parkinsonism dementia complex (GPDC) (Supplementary Table 2)
A consensus panel of 7 neuropathologists blinded to all clinical conditions and demographics evaluated the identical digitized images of 25 cases representing various tauopathies and concluded that the pathology of Chronic traumatic encephalopathy (CTE) is distinct from other tauopathies
Summary
In 1928, the pathologist and medical examiner, Harrison Stanford Martland, introduced the term ‘punch-drunk’ to describe the clinical features of a distinct neuropsychiatric syndrome that affected boxers [26]; a condition that later came to be known as ‘dementia pugilistica’ [33]. Case reports and small series describing the neuropathologic features of the condition appeared in the 1950s and 1960s [3, 6, 16, 27, 35, 41]. In the seminal 1973 monograph on the clinicopathological features of dementia pugilistica in 15 former male boxers, Corsellis, Bruton, and Freeman-Browne described cerebral atrophy, enlargement of the lateral and third ventricles, thinning of the corpus callosum, cavum. Department of Neuropathology, University of Glasgow Institute of Neuroscience and Psychology and Queen Elizabeth University Hospital, 1345 Govan Road, Glasgow G51 4TF, UK. Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue, Boston MA, 02118, USA. Department of Pathology, Fishberg Department of Neuroscience, Friedman Brain Institute, Ronald M.
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