Inflammatory biomarkers for neurobehavioral dysregulation in former American football players: findings from the DIAGNOSE CTE Research Project.

Autor: van Amerongen S; Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.; Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands.; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands., Pulukuri SV; Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Tuz-Zahra F; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA., Tripodis Y; Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.; Boston University Alzheimer's Disease Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Cherry JD; Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.; Boston University Alzheimer's Disease Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.; VA Boston Healthcare System, U.S. Department of Veteran Affairs, Boston, MA, USA.; Department of Veterans Affairs Medical Center, Bedford, MA, USA.; Department of Pathology and Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Bernick C; Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA., Geda YE; Department of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix, AZ, USA., Wethe JV; Department of Psychiatry and Psychology, Mayo Clinic School of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA., Katz DI; Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.; Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.; Brain Injury Program, Encompass Health Braintree Rehabilitation Hospital, Braintree, MA, USA., Alosco ML; Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.; Boston University Alzheimer's Disease Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.; Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Adler CH; Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA., Balcer LJ; Departments of Neurology, Population Health and Ophthalmology, NYU Grossman School of Medicine, New York, NY, USA., Ashton NJ; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.; Institute of Psychiatry, Psychology and Neuroscience, King's College London, Maurice Wohl Institute Clinical Neuroscience Institute, London, UK., Blennow K; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden., Zetterberg H; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.; Institute of Psychiatry, Psychology and Neuroscience, King's College London, Maurice Wohl Institute Clinical Neuroscience Institute, London, UK.; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.; UK Dementia Research Institute at UCL, London, UK.; Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53792, USA., Daneshvar DH; Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA., Colasurdo EA; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center, Seattle, WA, USA., Iliff JJ; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center, Seattle, WA, USA.; Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA., Li G; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center, Seattle, WA, USA.; Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA.; Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System Geriatric Research, Seattle, WA, USA., Peskind ER; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center, Seattle, WA, USA.; Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA., Shenton ME; Psychiatry Neuroimaging Laboratory, Harvard Medical School, Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Boston, MA, USA., Reiman EM; Banner Alzheimer's Institute, University of Arizona, Arizona State University, Translational Genomics Research Institute, and Arizona Alzheimer's Consortium, Phoenix, AZ, USA., Cummings JL; Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, NV, USA., Stern RA; Boston University CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA. bobstern@bu.edu.; Boston University Alzheimer's Disease Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA. bobstern@bu.edu.; Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA. bobstern@bu.edu.; Departments of Neurosurgery, and Anatomy and Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA. bobstern@bu.edu.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2024 Feb 09; Vol. 21 (1), pp. 46. Date of Electronic Publication: 2024 Feb 09.
DOI: 10.1186/s12974-024-03034-6
Abstrakt: Background: Traumatic encephalopathy syndrome (TES) is defined as the clinical manifestation of the neuropathological entity chronic traumatic encephalopathy (CTE). A core feature of TES is neurobehavioral dysregulation (NBD), a neuropsychiatric syndrome in repetitive head impact (RHI)-exposed individuals, characterized by a poor regulation of emotions/behavior. To discover biological correlates for NBD, we investigated the association between biomarkers of inflammation (interleukin (IL)-1β, IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-α) in cerebrospinal fluid (CSF) and NBD symptoms in former American football players and unexposed individuals.
Methods: Our cohort consisted of former American football players, with (n = 104) or without (n = 76) NBD diagnosis, as well as asymptomatic unexposed individuals (n = 55) from the DIAGNOSE CTE Research Project. Specific measures for NBD were derived (i.e., explosivity, emotional dyscontrol, impulsivity, affective lability, and a total NBD score) from a factor analysis of multiple self-report neuropsychiatric measures. Analyses of covariance tested differences in biomarker concentrations between the three groups. Within former football players, multivariable linear regression models assessed relationships among log-transformed inflammatory biomarkers, proxies for RHI exposure (total years of football, cumulative head impact index), and NBD factor scores, adjusted for relevant confounding variables. Sensitivity analyses tested (1) differences in age subgroups (< 60, ≥ 60 years); (2) whether associations could be identified with plasma inflammatory biomarkers; (3) associations between neurodegeneration and NBD, using plasma neurofilament light (NfL) chain protein; and (4) associations between biomarkers and cognitive performance to explore broader clinical symptoms related to TES.
Results: CSF IL-6 was higher in former American football players with NBD diagnosis compared to players without NBD. Furthermore, elevated levels of CSF IL-6 were significantly associated with higher emotional dyscontrol, affective lability, impulsivity, and total NBD scores. In older football players, plasma NfL was associated with higher emotional dyscontrol and impulsivity, but also with worse executive function and processing speed. Proxies for RHI exposure were not significantly associated with biomarker concentrations.
Conclusion: Specific NBD symptoms in former American football players may result from multiple factors, including neuroinflammation and neurodegeneration. Future studies need to unravel the exact link between NBD and RHI exposure, including the role of other pathophysiological pathways.
(© 2024. The Author(s).)
Databáze: MEDLINE
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