# Repetitive head injuries in German American football players do not change blood-based biomarker candidates for CTE during a single season

**Authors:** Theres Bastgen, Janis Evers, Christiane Oedekoven, Caroline Weide, Lars Herzog, Nicholas Ashton, Henrik Zetterberg, Kaj Blennow, Alexandra Albus, Natasha Vidovic, Oliver Kraff, Cornelius Deuschl, Richard Dodel, J. Alexander Ross

PMC · DOI: 10.1186/s42466-024-00307-6 · 2024-02-29

## TL;DR

This study finds that blood-based biomarkers for chronic traumatic encephalopathy (CTE) do not change significantly in American football players during a single season.

## Contribution

The study provides new evidence that CTE biomarker changes may occur slowly over multiple seasons or be detectable only in cerebrospinal fluid.

## Key findings

- Blood levels of CTE biomarkers like pTau, tTau, and GFAP did not change significantly in American football players during a single season.
- Players showed generally elevated pTau levels compared to controls.
- Correlations were found between biomarker levels and factors like depression, training participation, and concussion history.

## Abstract

Repetitive traumatic brain injuries in American football players (AFPs) can lead to the neurodegenerative disease chronic traumatic encephalopathy (CTE). Clinical symptoms of CTE range from mood and behavioral changes to cognitive impairment, depression, and suicidality. So far, CTE cannot be diagnosed in vivo and thus specific diagnostic parameters for CTE need to be found, to observe and treat exposed athletes as early as possible. Promising blood-based biomarkers for CTE include total tau (tTau), hyperphosphorylated tau (pTau), neurofilament light protein (NF-L), glial fibrillary acidic protein (GFAP), amyloid-β40 (Aβ40), amyloid-β42 (Aβ42) and calcium-binding protein B (S100-B). Previous studies have found elevated levels of these biomarkers in subjects exposed to TBIs, whereas cerebrospinal fluid (CSF) levels of Aβ40 and Aβ42 were decreased in CTE subjects. Here, we investigated whether young AFPs already exhibit changes of these biomarker candidates during the course of a single active season.

Blood samples were drawn from n = 18 American Football Players before and after a full season and n = 18 male age-matched control subjects. The plasma titers of tTau, pTau, NF-L, GFAP, Aβ40, Aβ42 and S100-B were determined. Additionally, Apathy, Depression, and Health status as well as the concussion history and medical care were assessed and analyzed for correlations.

Here we show, that the selected biomarker candidates for CTE do not change significantly during the seven-month period of a single active season of American Football in blood samples of AFPs compared to healthy controls. But interestingly, they exhibit generally elevated pTau titers. Furthermore, we found correlations of depression, quality-of-life, career length, training participation and training continuation with headache after concussion with various titers.

Our data indicates, that changes of CTE marker candidates either occur slowly over several active seasons of American Football or are exclusively found in CSF. Nevertheless, our results underline the importance of a long-term assessment of these biomarker candidates, which might be possible through repeated blood biomarker monitoring in exposed athletes in the future.

The online version contains supplementary material available at 10.1186/s42466-024-00307-6.

## Linked entities

- **Proteins:** Mapt (microtubule-associated protein tau), NEFL (neurofilament light chain), GFAP (glial fibrillary acidic protein), S100B (S100 calcium binding protein B)
- **Diseases:** chronic traumatic encephalopathy (MONDO:0019976), depression (MONDO:0002050)

## Full-text entities

- **Genes:** NEFL (neurofilament light chain) [NCBI Gene 4747] {aka CMT1F, CMT2E, CMTDIG, NF-L, NF68, NFL}, S100B (S100 calcium binding protein B) [NCBI Gene 6285] {aka NEF, S100, S100-B, S100beta}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, GFAP (glial fibrillary acidic protein) [NCBI Gene 2670] {aka ALXDRD}
- **Diseases:** head injuries (MESH:D006259), concussion (MESH:D001924), Depression (MESH:D003866), cognitive impairment (MESH:D003072), neurodegenerative disease (MESH:D019636), CTE (MESH:D000070627), headache (MESH:D006261), TBIs (MESH:D000070642)
- **Chemicals:** pTau (-)

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC10903054/full.md

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Source: https://tomesphere.com/paper/PMC10903054