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Brief Report
January 6, 2020

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

Author Affiliations
  • 1Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco
  • 2Department of Pathology, University of California, San Francisco, San Francisco
  • 3Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California
  • 4Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco
  • 5Associate Editor, JAMA Neurology
JAMA Neurol. Published online January 6, 2020. doi:10.1001/jamaneurol.2019.4509
Key Points

Question  Does in vivo binding of the tau positron emission tomography radioligand fluorine F 18–labeled (18F)–flortaucipir correspond to tau pathology in chronic traumatic encephalopathy?

Findings  In a patient with pathologically confirmed chronic traumatic encephalopathy, 18F-flortaucipir positron emission tomography performed 52 months prior to death showed a patchy, frontotemporal pattern corresponding qualitatively to regions with tau pathology found at autopsy. There was a modest correlation between regional 18F-flortaucipir standardized uptake value ratios and tau immunohistochemistry area fraction that did not reach statistical significance.

Meaning  Findings in this case suggest that 18F-flortaucipir may have limited utility as a biomarker of tau pathology in chronic traumatic encephalopathy.

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.

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