Tau Positron Emission Tomographic Findings in a Former US Football Player with Pathologically Confirmed Chronic Traumatic Encephalopathy

William G. Mantyh, Salvatore Spina, Alex Lee, Leonardo Iaccarino, David Soleimani-Meigooni, Elena Tsoy, Taylor J. Mellinger, Harli Grant, Lawren Vandevrede, Renaud La Joie, Orit Lesman-Segev, Stephanie Gaus, Katherine L. Possin, Lea T. Grinberg, Bruce L. Miller, William W. Seeley, Gil D. Rabinovici

Research output: Contribution to journalArticlepeer-review

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Abstract

Importance: Biomarkers for chronic traumatic encephalopathy (CTE) are currently lacking. The radiotracer fluorine F 18-labeled (18F)-flortaucipir (FTP) detects tau pathology in Alzheimer disease, and positron emission tomography (PET) with FTP shows elevated binding in individuals at risk for CTE. No study, however, has assessed the correlation between in vivo FTP PET and postmortem tau in CTE. Objective: To assess the regional association between in vivo FTP binding and postmortem tau pathology in a patient with pathologically confirmed CTE. Design, Setting, and Participants: A white male former National Football League player with 17 years of US football exposure was clinically diagnosed with traumatic encephalopathy syndrome at a neurology tertiary referral center. 18F-Fludeoxyglucose, carbon 11-labeled Pittsburgh compound B, and FTP PET were performed 52 months prior to death, and magnetic resonance imaging, 50 months prior to death. Brain images were assessed qualitatively for abnormalities blinded to autopsy data. Autopsy was performed using a neurodegenerative research protocol. The FTP standardized uptake value ratios (inferior cerebellar gray reference region) and W-score (age-adjusted z-score) maps were compared with phosphorylated tau immunohistochemical analysis with monoclonal antibody CP13. Main Outcomes and Measures: Qualitative and quantitative comparisons between antemortem FTP PET and tau pathology at autopsy. Results: Flortaucipir uptake was distributed in a patchy, frontotemporal-predominant pattern that overlapped with regions showing neurodegeneration on magnetic resonance imaging and hypometabolism on 18F-fludeoxyglucose PET. Pathological assessment revealed stage 4 CTE; limbic argyrophilic grain disease; stage 2 limbic-predominant, age-related transactive response DNA-binding protein 43 encephalopathy; and Braak neurofibrillary tangle stage 3. 18F-Flortaucipir W-maps matched areas of high postmortem tau burden in left fusiform and inferior temporal gyri and juxtacortical frontal white matter. High FTP W-scores with low tau burden were found in the basal ganglia, thalamus, motor cortex, and calcarine cortex. No regions with low FTP W-scores corresponded to areas with high pathological tau burden. A modest correlation, which did not reach statistical significance (ρ = 0.35, P =.17), was found between FTP standardized uptake value ratio and tau area fraction at the regional level. Conclusions and Relevance: In this patient, FTP PET findings during life showed a modest correspondence with postmortem pathology in CTE. These findings suggest that FTP may have limited utility as a tau biomarker in CTE.

Original languageEnglish (US)
Pages (from-to)517-521
Number of pages5
JournalJAMA Neurology
Volume77
Issue number4
DOIs
StatePublished - Apr 2020

Bibliographical note

Funding Information:
Soleimani-Meigooni reported receiving a grant from the Alzheimer’s Association during the conduct of the study. Dr Possin reported receiving grants from Global Brain Health Institute and the National Institute of Neurological Disorders and Stroke during the conduct of the study and grants from Quest Diagnostics, Merck Foundation, the National Institute on Aging, and the Centers for Medicare and Medicaid Innovation outside the submitted work. Dr Grinberg reported receiving grants from the National Institutes of Health (NIH), Avid Radiopharmaceuticals, and Eli Lilly and Company during the conduct of the study. Dr Seeley reported receiving grants from the NIH during the conduct of the study. Dr Rabinovici reported receiving grants from the NIH and from Tau Consortium during the conduct of the study; grants from Avid Radiopharmaceuticals, Eli Lilly and Company, GE Healthcare, and Life Molecular Imaging outside the submitted work; and personal fees from GE Healthcare, Axon Neurosciences, Merck, Eisai, Roche, and Genentech outside the submitted work. No other disclosures were reported.

Funding Information:
Funding/Support: This work was funded by

Funding Information:
National Institutes of Health grants P50AG023501 (Drs Miller and Rabinovici) and K08AG052648 (Dr Spina), a Robert W. Katzman Fellowship Training Grant through the American Academy of Neurology in conjunction with the American Brain Foundation and Alzheimer’s Association (Dr Mantyh), an Alzheimer’s Association Research Fellowship 16-443577 (Dr La Joie), and a grant from the Tau Consortium (Dr Rabinovici).

PubMed: MeSH publication types

  • Case Reports
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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