PET Scan Not Effective for Diagnosis of CTE

January 09, 2020

An imaging test targeting the tau protein that has been shown accurate for the diagnosis of Alzheimer's disease is probably not suitable for detecting chronic traumatic encephalopathy (CTE), another condition characterized by tau accumulation, new data suggest.

The results come from a comparison of the in-vivo binding of the tau positron emission tomography (PET) radioligand fluorine F18–labeled flortaucipir (FTP) with tau pathology on post-mortem in the same patient, which only showed modest correlation.    

The report was published online January 6 in JAMA Neurology.

Lead author William G. Mantyh, MD, University of California San Francisco Memory and Aging Center, explained to Medscape Medical News that CTE is a delayed phenomenon that can occur in later life in individuals who have suffered repetitive head trauma in younger life. For example, an American football player who stopped playing in his 30s may develop the condition in his 60s or 70s.

"CTE is difficult to diagnose as it has widely variable clinical symptoms, including cognitive, behavioral, and motor issues and can be confused with Alzheimer's, Parkinson's, or other neurological conditions," Mantyh noted.

He also pointed out that the prevalence of CTE is unknown. "We really don't know how many people may be harboring the condition, but many young people play football or other contact sports in their younger years. This is a relatively recently discovered condition. We've only started looking for it in the last few years and we don’t know much about it or how prevalent it is."

At present, CTE can only be properly diagnosed after death by examining the pathology of the brain, with hyperphosphorylated tau present around the blood vessels in the cortical sulci — regions between cortical folds embedded in the surface of the brain, which is where the shearing forces are felt most acutely in head trauma.

It is this specific location of tau that is crucial for the CTE diagnosis, Mantyh said, "but we really need a test that can confidently diagnose CTE during life."

The current report focuses on a white male former National Football League player with 17 years of US football exposure who was exhibiting symptoms of traumatic encephalopathy syndrome.

An FTP PET scan was performed 52 months prior to death, and MRI was performed 50 months prior to death. Brain images were assessed qualitatively for abnormalities blinded to autopsy data.

"We found a modest correlation of FTP PET and tau on post-mortem which was not statistically significant. The degree of binding was much lower than seen in Alzheimer's disease. This is probably because the actual detailed structure of tau is thought to be different in CTE and Alzheimer's," Mantyh said.

"Our results did not show enough correlation to suggest that this would be an effective diagnostic test for CTE."

However, he pointed out that this study was conducted in just one patient, which is a major limitation. "There may be different structural variants of tau in different CTE patients and we might not have sampled the exact correct locations in the brain in the post-mortem study to pick up the true correlation."

Mantyh said that although these results are a little disappointing, they will help in developing future research strategies. 

"We need more focused development of a ligand specific for the CTE form of tau. There are some really promising new blood tests for tau in Alzheimer’s disease in development which will be much more convenient than a PET scan and will hopefully revolutionize the field. I believe it is only a matter of time until something similar is developed for the CTE-specific type of tau."

Commenting on the current report for Medscape Medical News, Sarah Benish, MD, associate professor of neurology at the University of Minnesota in Minneapolis, said: "I conclude from this article that FTP PET still does not have a clear clinical role to help diagnose CTE in life and I would not offer it to my patients in the office setting."

"There is some promise here, but the concept needs more research with perhaps a larger sampling of patients to look for false positive and false negatives," said Benish, a fellow of the American Academy of Neurology who was not involved with the study.  

This work was funded by grants from the National Institutes of Health, the American Academy of Neurology/American Brain Foundation/Alzheimer’s Association, the Tau Consortium, and an Alzheimer’s Association Research Fellowship. Mantyh and Benish have disclosed no relevant financial relationships.

JAMA Neurol. Published online January 6, 2020. Abstract  

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