06 Jan Tau Pet Scanning In a Former NFL Play with CTE

MedicalResearch.com Interview with:

Dr. Mantyh

William G. Mantyh, MD
Clinical Fellow, UCSF Memory and Aging Center
Weill Institute for Neurosciences
UCSF

MedicalResearch.com: What is the background for this study?

Response: Similar to Alzheimer’s disease (AD) and other dementing illnesses, Chronic Traumatic Encephalopathy (CTE) is a progressive neurodegenerative condition associated with abnormally folded tau protein in the brain. CTE is thought to be caused by exposure to repetitive head trauma, and recently has been the subject of intense media coverage given the frequency of CTE found in brains of deceased former American professional football players. CTE is almost impossible to confidently diagnose during life as the symptoms are diverse and vary from patient-to-patient. Symptoms can include impairments in memory, multi-tasking, behavioral/mood regulation, and movement. As there are no blood, imaging, or other tests for this disease, one active area of research is developing a test to help doctors diagnose this condition.

As tau tangles in CTE are similar in many respects to those in Alzheimer’s disease, there was hope that PET tracers that detect tau in AD might also work in CTE. Flortaucipir (FTP) is probably the most widely used tau tracer in AD. Recent work has reported some signal from FTP-PET in symptomatic former NFL players and other patients at risk for CTE (Stern et al. New Engl Jour Med 2019; Lesman-Segev et al. Neuroimage Clinical 2019). The overall signal was lower than that observed in Alzheimer’s disease, and, in lieu of correlations with post-mortem findings, it was unclear how well FTP binds to tau pathology in CTE.

MedicalResearch.com: What are the main findings?

Response: In the present report, we examined whether FTP correlated to the amount of misfolded tau protein found at autopsy in a former American football player suffering from CTE. This is the first report in the literature describing PET-to-autopsy correlations in a patient with CTE. We found that FTP-PET during life showed only a modest correlation with tau pathology found at autopsy four years later. While this is a single case report, it does raise concerns that FTP may not reliably detect tau pathology in CTE.

MedicalResearch.com: What should readers take away from your report?

Response: Given the difficulty of diagnosing CTE during life, CTE remains a diagnosis that relies on postmortem examination. Novel blood, cerebrospinal fluid, or neuroimaging tests are areas of active research and will likely make great headway into our future ability to diagnose this condition. Finally, if our results are replicated in other patients, we will likely need different PET tracers to accurately measure tau pathology in CTE. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Although CTE was first described 100 years ago (with a different name at the time — “Punch Drunk syndrome”), research in this field is still in its infancy. Novel ultra-sensitive bioassays, neuroimaging techniques, and genetic/protein/metabolite studies are poised to greatly expand our knowledge of this disease.

MedicalResearch.com: Is there anything else you would like to add? 

Response: Head trauma, the upstream event leading to CTE, also is known to predispose to many other neurodegenerative diseases. Better understanding CTE may also help our understanding of how diseases like Alzheimer’s, Parkinson’s, or Frontotemporal dementia develop. CTE research thus may accelerate the pace of discovering disease mechanisms and drug targets for a variety of dementing illnesses.

I have no disclosures. Avid Radiopharmaeuticals, a wholly owned subsidiary of Eli Lilly, hold the license and enabled the use of the FTP tracer, but had no role in study design, funding, interpretation or reporting.

Citation:

Mantyh WG, Spina S, Lee A, et al. Tau Positron Emission Tomographic Findings in a Former US Football Player With Pathologically Confirmed Chronic Traumatic Encephalopathy. JAMA Neurol. Published online January 06, 2020. doi:https://doi.org/10.1001/jamaneurol.2019.4509

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Last Updated on January 6, 2020 by Marie Benz MD FAAD