Home › Research › Getting a diagnosis
The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy
McKee AC, Cairns NJ, Dickson DW, Folkerth RD, Keene CD, Litvan I, Perl DP, Stein TD et al.. Acta neuropathologica, 2015-12-14
Topic: Brain proteins, microglia and lab models
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.
Key findings
- 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.
Why it matters
In this first NINDS/NIBIB consensus panel, 7 neuropathologists used preliminary criteria to blindly review 25 brains with different tau diseases, including CTE and Alzheimer's, and agreed well (Cohen's kappa 0.67; 0.78 against the CTE diagnosis). The panel defined CTE's tell-tale lesion as abnormal tau in nerve and support cells clustered around small blood vessels deep in the brain's folds, and set a minimum tissue-sampling and staining scheme. The criteria apply only to brain tissue examined after death, are described as a "first step" toward validated criteria, and say nothing about treating or preventing Alzheimer's disease.
New to this subject? Start with our plain-English guide: Getting a diagnosis →
Study details
- Evidence strengthLow
How this study scored 61/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Acta neuropathologica) |
| Journal's citation record | 3 / 4 | Acta Neuropathologica: journal h-index 287 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 887 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 73.9 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 6 / 6 | Cited 56.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 35 other studies in this library |
| Still being cited | 3 / 4 | Cited 179 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Wayne A. Gordon: h-index 66 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 19 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26667418) |
| Free to read | 2 / 2 | Free to read |
| Total | 61 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1007/s00401-015-1515-z
- PubMed: 26667418
- Original source →
- Free full text: Acta Neuropathologica →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
McKee, A. C., Cairns, N. J., Dickson, D. W., Folkerth, R. D., Keene, C. D., Litvan, I., et al. (2016). The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy. Acta neuropathologica. https://doi.org/10.1007/s00401-015-1515-z
Vancouver
McKee AC, Cairns NJ, Dickson DW, Folkerth RD, Keene CD, Litvan I, et al. The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy. Acta neuropathologica. 2016. doi:10.1007/s00401-015-1515-z. PMID: 26667418.
BibTeX
@article{mckee2016-26667418,
author = {McKee, A. C. and Cairns, N. J. and Dickson, D. W. and Folkerth, R. D. and Keene, C. D. and Litvan, I. and Perl, D. P. and Stein, T. D. and others},
title = {{The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy}},
journal = {Acta neuropathologica},
year = {2016},
doi = {10.1007/s00401-015-1515-z},
pmid = {26667418},
url = {https://doi.org/10.1007/s00401-015-1515-z}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
35 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Getting a diagnosis
Also tagged “cerebral”
900 studies in the library carry the topic tag “cerebral”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 900 tagged studies.