title: The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy.
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.
authors.affiliation: Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. amckee@bu.edu.|Department of Pathology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. amckee@bu.edu.|Alzheimer's Disease Center, CTE Program, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. amckee@bu.edu.|VA Boston Healthcare System, 150 South Huntington Avenue, Boston, 02130, MA, USA. amckee@bu.edu.|Department of Veteran Affairs Medical Center, 200 Springs Road, Bedford, MA, 01730, USA. amckee@bu.edu.
authors.forename: Ann C
authors.initials: AC
authors.lastname: McKee
authors.affiliation: Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, Saint Louis, MO, 63110, USA.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
authors.affiliation: Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Folkerth
authors.affiliation: Department of Pathology, University of Washington School of Medicine, 325 Ninth Avenue, Seattle, WA, 98104, USA.
authors.forename: C Dirk
authors.initials: CD
authors.lastname: Keene
authors.affiliation: Department of Neurosciences, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
authors.forename: Irene
authors.initials: I
authors.lastname: Litvan
authors.affiliation: Department of Pathology, Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Perl
authors.affiliation: Department of Pathology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA.|Alzheimer's Disease Center, CTE Program, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA.|VA Boston Healthcare System, 150 South Huntington Avenue, Boston, 02130, MA, USA.|Department of Veteran Affairs Medical Center, 200 Springs Road, Bedford, MA, 01730, USA.
authors.forename: Thor D
authors.initials: TD
authors.lastname: Stein
authors.affiliation: 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.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vonsattel
authors.affiliation: Department of Neuropathology, University of Glasgow Institute of Neuroscience and Psychology and Queen Elizabeth University Hospital, 1345 Govan Road, Glasgow, G51 4TF, UK.
authors.forename: William
authors.initials: W
authors.lastname: Stewart
authors.affiliation: Alzheimer's Disease Center, CTE Program, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA.|Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue, Boston, MA, 02118, USA.
authors.forename: Yorghos
authors.initials: Y
authors.lastname: Tripodis
authors.affiliation: 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.
authors.forename: John F
authors.initials: JF
authors.lastname: Crary
authors.affiliation: Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Bieniek
authors.affiliation: Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai, 3 East 101st Street, New York, NY, 10029, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Dams-O'Connor
authors.affiliation: Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA.|Department of Pathology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA.|Alzheimer's Disease Center, CTE Program, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA.|VA Boston Healthcare System, 150 South Huntington Avenue, Boston, 02130, MA, USA.
authors.forename: Victor E
authors.initials: VE
authors.lastname: Alvarez
authors.affiliation: Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai, 3 East 101st Street, New York, NY, 10029, USA.
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Gordon
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D001344:Autopsy; D020208:Brain Injury, Chronic / Q000175:diagnosis* / Q000503:physiopathology; D006801:Humans; D054581:National Institute of Biomedical Imaging and Bioengineering (U.S.); D055825:National Institute of Neurological Disorders and Stroke (U.S.); D016874:Neurofibrillary Tangles / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D024801:Tauopathies / Q000473:pathology; D014481:United States; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016875:tau Proteins
keywords: Brain trauma; Chronic traumatic encephalopathy; Neurodegenerative disorders; Tauopathy; Traumatic brain injury