Anna Vasilevskaya1,2,3,4, Foad Taghdiri1,3,4, Namita Multani1,3, Miracle Ozzoude1, Apameh Tarazi3,4, Mozhgan Khodadadi4, Richard Wennberg3,4, Pablo Rusjan5,6, Sylvain Houle7, Robin Green4,8, Brenda Colella4,8, Kaj Blennow9,10, Henrik Zetterberg9,10,11,12, Thomas Karikari9, David Mikulis2,4,13, Lili-Naz Hazrati4,14, Gabor G Kovacs1,15,16, Karen Deborah Davis2,4,17, Charles Tator2,4,18, Maria Carmela Tartaglia19,20,21,22. 1. Tanz Centre for Research in Neurodegenerative Diseases, Krembil Discovery Tower, University of Toronto, 60 Leonard Avenue, 6th floor 6KD-407, Toronto, ON, M5T 2S8, Canada. 2. Institute of Medical Science, University of Toronto, Toronto, ON, Canada. 3. Division of Neurology, Toronto Western Hospital, University Health Network, Toronto, ON, Canada. 4. Krembil Neuroscience Centre, Canadian Concussion Center, Toronto Western Hospital, University Health Network, Toronto, ON, Canada. 5. Douglas Mental Health University Institute, Montreal, QC, Canada. 6. Department of Psychiatry, McGill University, Montreal, QC, Canada. 7. Brain Health Imaging Centre, Campbell Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada. 8. KITE Research Institute, University Health Network, Toronto, ON, Canada. 9. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. 10. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 11. Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK. 12. UK Dementia Research Institute at UCL, London, UK. 13. Division of Neuroradiology, Joint Department of Medical Imaging, University Health Network, Toronto, ON, Canada. 14. Pathology, The Hospital for Sick Children, Toronto, ON, Canada. 15. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. 16. Laboratory Medicine Program and Krembil Brain Institute, University Health Network, Toronto, ON, Canada. 17. Department of Surgery, University of Toronto, Toronto, ON, Canada. 18. Division of Neurosurgery, Krembil Brain Institute, Toronto Western Hospital, University Health Network, Toronto, ON, Canada. 19. Tanz Centre for Research in Neurodegenerative Diseases, Krembil Discovery Tower, University of Toronto, 60 Leonard Avenue, 6th floor 6KD-407, Toronto, ON, M5T 2S8, Canada. carmela.tartaglia@uhn.ca. 20. Institute of Medical Science, University of Toronto, Toronto, ON, Canada. carmela.tartaglia@uhn.ca. 21. Division of Neurology, Toronto Western Hospital, University Health Network, Toronto, ON, Canada. carmela.tartaglia@uhn.ca. 22. Krembil Neuroscience Centre, Canadian Concussion Center, Toronto Western Hospital, University Health Network, Toronto, ON, Canada. carmela.tartaglia@uhn.ca.
Abstract
BACKGROUND: Considering the wide range of outcomes following sport-related concussions, biomarkers are needed to detect underlying pathological changes. The objective was to analyze the use of plasma phosphorylated tau 181 (pTau181) as a non-invasive measure of underlying brain changes in a cohort of retired contact sports athletes at risk of neurodegeneration. METHODS: Fifty-four retired contact sport athletes and 27 healthy controls whose blood plasma was analyzed for pTau181 were included. A portion (N = 21) of retired athletes had a 2-years follow-up visit. All participants had completed a neuropsychological battery and MRI imaging. RESULTS: Plasma pTau181 was significantly higher in retired athletes compared to healthy controls (8.94 ± 5.08 pg/mL vs. 6.00 ± 2.53 pg/mL, respectively; 95% BCa CI 1.38-4.62; p = 0.02); and was significantly associated with fornix fractional anisotropy values only in the athletes group (β = - 0.002; 95% BCa CI - 0.003 to - 0.001; p = 0.002). When the retired athletes cohort was divided into high vs. normal pTau181 groups, the corpus callosum (CC) volume and white-matter integrity was significantly lower in high pTau181 compared to older healthy controls (CC volume: 1.57 ± 0.19 vs. 2.02 ± 0.32, p = 0.002; CC medial diffusivity: 0.96 ± 0.04 × 10-3 mm2/s vs. 0.90 ± 0.03 × 10-3 mm2/s, p = 0.003; CC axial diffusivity: 1.49 ± 0.04 × 10-3 mm2/s vs. 1.41 ± 0.02 × 10-3 mm2/s, p < 0.001, respectively). CONCLUSIONS: Although high plasma pTau181 levels were associated with abnormalities in CC and fornix, baseline pTau181 did not predict longitudinal changes in regional brain volumes or white-matter integrity in the athletes. pTau181 may be useful for identifying those with brain abnormalities related to repeated concussion but not for predicting progression.
BACKGROUND: Considering the wide range of outcomes following sport-related concussions, biomarkers are needed to detect underlying pathological changes. The objective was to analyze the use of plasma phosphorylated tau 181 (pTau181) as a non-invasive measure of underlying brain changes in a cohort of retired contact sports athletes at risk of neurodegeneration. METHODS: Fifty-four retired contact sport athletes and 27 healthy controls whose blood plasma was analyzed for pTau181 were included. A portion (N = 21) of retired athletes had a 2-years follow-up visit. All participants had completed a neuropsychological battery and MRI imaging. RESULTS: Plasma pTau181 was significantly higher in retired athletes compared to healthy controls (8.94 ± 5.08 pg/mL vs. 6.00 ± 2.53 pg/mL, respectively; 95% BCa CI 1.38-4.62; p = 0.02); and was significantly associated with fornix fractional anisotropy values only in the athletes group (β = - 0.002; 95% BCa CI - 0.003 to - 0.001; p = 0.002). When the retired athletes cohort was divided into high vs. normal pTau181 groups, the corpus callosum (CC) volume and white-matter integrity was significantly lower in high pTau181 compared to older healthy controls (CC volume: 1.57 ± 0.19 vs. 2.02 ± 0.32, p = 0.002; CC medial diffusivity: 0.96 ± 0.04 × 10-3 mm2/s vs. 0.90 ± 0.03 × 10-3 mm2/s, p = 0.003; CC axial diffusivity: 1.49 ± 0.04 × 10-3 mm2/s vs. 1.41 ± 0.02 × 10-3 mm2/s, p < 0.001, respectively). CONCLUSIONS: Although high plasma pTau181 levels were associated with abnormalities in CC and fornix, baseline pTau181 did not predict longitudinal changes in regional brain volumes or white-matter integrity in the athletes. pTau181 may be useful for identifying those with brain abnormalities related to repeated concussion but not for predicting progression.
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