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Plasma Total-Tau Level May Flag CTE

Lack of Biomarker Frustrates CTE researchers

From MedPage Today | By Mike Bassett

BOSTON — Repeated head impact (RHI) exposure predicts higher later-life plasma total-tau (t-tau) concentrations in former professional football players, suggesting that t-tau could be a candidate screening biomarker for chronic traumatic encephalopathy (CTE), researchers reported here at the annual meeting of the American Academy of Neurology.

Since the discovery of this progressive degenerative disease, what has frustrated CTE researchers is that CTE can currently only be diagnosed after death by postmortem neuropathological analysis.

“One of the problems is that we don’t have any biomarkers to detect the presence of CTE in life,” said Michael L. Alosco, PhD., of the Boston University Alzheimer's Disease and CTE Center, and lead author of the study.

While a number of potential neuroimaging biomarkers for CTE (such as volumetric MRI, diffusion-tension imaging, or MR spectroscopy) have been identified, Alosco and his colleagues pointed out that none these methods can assess the pathology underlying CTE.

There is an expectation that positron-emission tomography could eventually serve as the gold standard biomarker for CTE, but it exposes patients to radiation, and is both expensive and time-consuming. And although cerebrospinal fluid protein markers of neurodegeneration are accepted alternatives to PET, it involves a lumbar puncture, which many patients fear.

“Plasma analysis of blood analysis of tau protein is noninvasive and inexpensive,” said Alosco, and could be a very effective way of screening for CTE in life.

In this study, the researchers wanted to examine plasma t-tau concentrations in former National Football League players at risk for CTE and compare them to a same-age control group.

For the study, ninety-six symptomatic former NFL players (ages 40-69) and 25 same-age controls had blood drawn and completed neuropsychological and neuropsychiatric testing.

A cumulative head impact index (CHII), which is derived from self-reported football histories, including number of years and positions played, as well as the estimated head impact frequencies, was used to quantify RHI exposure in the former football players.

“We found a significant correlation between the CHII and plasma total tau, such that more hits to the head was associated with greater concentrations of higher levels of total tau in the blood,” said Alosco.

The researchers found that the mean plasma t-tau concentrations in former NFL players was 2.53 (1.01) pg/mL compared to 2.45 (0.57) pg/mL, a nonsignificant difference when controlled for age.

However, the former NFL players had a significantly greater range of t-tau levels compared to the controls, with the former players tending to have t-tau values in the higher end of the range. Furthermore, a plasma t-tau level of 3.56 pg/mL or greater was found in 12 of the former players, while no controls had levels that high.

There was also a significant correlation between plasma t-tau levels and the CHII in the former football players, with greater exposure to RHI associated with higher concentrations of plasma t-tau. Of great significance, said Alosco, was a finding that the 12 former players with the ≥3.56 pg/mL had a higher CHII than the remaining members of the group when controlling for age and body mass index.

The ≥3.56 pg/mL level cutoff that was specific to the 12 former NFL players “was specific, but not sensitive, and optimally you want a specific and sensitive biomarker” said Alosco.

Still, “the study provides additional evidence for us to continue to explore plasma total tau as a potential biomarker for neurodegenerative diseases — CTE in this case,” Alosco concluded. “So we need to be able to repeat this study once we can clinically diagnose CTE during life, which is what we are studying at the Alzheimer's Disease and CTE Center at BU.”

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