PET Scan May Detect CTE in Living Athletes

Megan Brooks

May 06, 2015

Positron emission tomography (PET) using the investigational tau tracer FDDNP may reveal chronic traumatic encephalopathy (CTE) in living athletes and differentiate it from Alzheimer's disease (AD), new research hints.

Detecting CTE early "would facilitate the most effective management strategies and provide a baseline to measure the effectiveness of treatments," the investigators say.

CTE is an acquired primary tauopathy characterized by cognitive, behavior, and mood changes. A history of repetitive concussions sustained in contact sports, such as football and boxing, is the strongest risk factor (to date) for CTE. However, there is no definitive approach for clinically diagnosing the condition in living humans. Currently, CTE can be diagnosed definitively only at autopsy.

In an earlier study, Jorge Barrio, PhD, from University of California, Los Angeles (UCLA), and colleagues found that tau protein deposits seen on FDDNP PET were higher in all subcortical regions and in the amygdala in five retired National Football League (NFL) players compared with controls.

In their latest study, they found the same characteristic pattern of tau accumulation in these regions in 14 retired football players suspected of having CTE and also showed that the pattern differed markedly from findings in 28 cognitively normal controls and 24 patients with AD.


The study was published online April 6 in Proceedings of the National Academy of Science of the United States of America.

Distinct Pattern

The FDDNP PET imaging results in the 14 retired football players point to the presence of neuropathologic patterns "consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior," the investigators write.

"This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-β] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures," they point out.

They also note that the pattern seen in living athletes suspected of having CTE mirrors PHF-tau distribution seen at autopsy in individuals with a history of mild traumatic brain injury and autopsy-confirmed CTE.

"The distribution pattern of the abnormal brain proteins, primarily tau, observed in these PET scans, presents a 'fingerprint' characteristic of CTE," Dr Barrio said in a UCLA news release.

"These results suggest that this brain scan may also be helpful as a test to differentiate trauma-related cognitive issues from those caused by [AD]," added Julian Bailes, MD, director, Brain Injury Research Institute, Northshore University HealthSystem, Evanston, Illinois, who worked on the study.

"Important" Research

This study "sets the stage for better diagnostics and ultimately better therapeutics," Richard Lipton, MD, director, Division of Cognitive Aging and Dementia at Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York, who wasn't involved in the study, noted in an interview with Medscape Medical News.

Dr Lipton thinks the study and this line of research are important for three reasons. "First, not everybody who played football and has a cognitive impairment has CTE; some people might have Parkinson's or Alzheimer's or some other etiology, so this lends a level of diagnostic confidence. Because the pattern differs with CTE, that would make it useful diagnostically."

Second, "it could turn out, and this hasn't been shown yet, that abnormal tau accumulates early in people who may be heading for trouble with repeated traumatic brain injury and that might allow either preventive intervention, like stop playing football," he said. "As a neurologist, I have long been opposed to voluntary head trauma. If we were able to show that some people were getting into trouble with either cognitive decline or abnormal tau accumulation in the brain, that might motivate people to modify their risk factors."

Third, "if accumulation of tau is in the pathway that links head injury to cognitive decline and other clinical symptoms then we might be able to use it as a marker for treatment," Dr Lipton said. If tau-directed therapies are developed that prevent tau from accumulating or increase its removal from the brain, "this imaging method might be useful to demonstrate that treatments are doing what we hope they do," he noted.

The FDDNP marker is intellectual property owned by UCLA and licensed to TauMark, LLC. Three UCLA investigators — Dr Barrio, Gary Small, MD, and Sung-Cheng Huang, DSc — are co-inventors of the PET marker. Dr Barrio and Dr Small have a financial interest in the company.

In February, the US Food and Drug Administration's (FDA's) Office of Prescription Drug Promotion sent a letter to Dr Barrio and Dr Small warning that they had improperly promoted FDDNP, an investigational drug, on their website (taumark.com) and had overstated claims about its potential efficacy, "when FDA has not approved FDDNP for any use."

In a statement responding to the FDA letter, UCLA said, "As soon as UCLA recognized that the IND [investigational new drug] had not been transferred to the company (TauMark) when the technology was licensed from UCLA, that was corrected. Additionally, although UCLA did not control TauMark's website, UCLA instructed TauMark to refrain from activities that would constitute impermissible commercialization.

"The researchers did have IRB [institutional review board] approval for the study. The campus has well established policies and processes for soliciting disclosures of financial interests, reviewing them, and managing identified financial conflicts of interest related to research."

The study was supported by grants from the National Institutes of Health and gifts to UCLA from the Toulmin Foundation and Robert and Marion Wilson. No company provided funding for this study. Dr Barrio has a financial interest in TauMark, LLC.

Proc Natl Acad Sci U S A. Published online April 6, 2015. Abstract

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