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Acta Neuropathol. 2016 Jan;131(1):75-86. doi: 10.1007/s00401-015-1515-z. Epub 2015 Dec 14.

The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy.

Author information

1
Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. amckee@bu.edu.
2
Department of Pathology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. amckee@bu.edu.
3
Alzheimer's Disease Center, CTE Program, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. amckee@bu.edu.
4
VA Boston Healthcare System, 150 South Huntington Avenue, Boston, 02130, MA, USA. amckee@bu.edu.
5
Department of Veteran Affairs Medical Center, 200 Springs Road, Bedford, MA, 01730, USA. amckee@bu.edu.
6
Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, Saint Louis, MO, 63110, USA.
7
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
8
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
9
Department of Pathology, University of Washington School of Medicine, 325 Ninth Avenue, Seattle, WA, 98104, USA.
10
Department of Neurosciences, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
11
Department of Pathology, Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
12
Department of Pathology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA.
13
Alzheimer's Disease Center, CTE Program, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA.
14
VA Boston Healthcare System, 150 South Huntington Avenue, Boston, 02130, MA, USA.
15
Department of Veteran Affairs Medical Center, 200 Springs Road, Bedford, MA, 01730, USA.
16
Taub Institute for Research on Alzheimer's disease and the Aging Brain, Columbia University Medical Center, 710 West 168th Street, New York, NY, 10032, USA.
17
Department of Neuropathology, University of Glasgow Institute of Neuroscience and Psychology and Queen Elizabeth University Hospital, 1345 Govan Road, Glasgow, G51 4TF, UK.
18
Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue, Boston, MA, 02118, USA.
19
Department of Pathology, Fishberg Department of Neuroscience, Friedman Brain Institute, Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai School, One Gustave L. Levy Place, New York, NY, 10029, USA.
20
Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai, 3 East 101st Street, New York, NY, 10029, USA.
21
Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA.

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.

KEYWORDS:

Brain trauma; Chronic traumatic encephalopathy; Neurodegenerative disorders; Tauopathy; Traumatic brain injury

PMID:
26667418
PMCID:
PMC4698281
DOI:
10.1007/s00401-015-1515-z
[Indexed for MEDLINE]
Free PMC Article

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