{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:46:08Z","timestamp":1790178368262,"version":"4.1.0"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1127007"],"award-info":[{"award-number":["APP1127007"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1104692"],"award-info":[{"award-number":["APP1104692"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Blood biomarkers are an emerging diagnostic and prognostic tool that reflect a range of neuropathological processes following traumatic brain injury (TBI). Their effectiveness in identifying long-term neuropathological processes after TBI is unclear. Studying biomarkers in the chronic phase is vital because elevated levels in TBI might result from distinct neuropathological mechanisms during acute and chronic phases. Here, we examine plasma biomarkers in the chronic period following TBI and their association with amyloid and tau PET, white matter microarchitecture, brain age and cognition.<\/jats:p>\n                  <jats:p>We recruited participants \u226540 years of age who had suffered a single moderate\u2013severe TBI \u226510 years previously between January 2018 and March 2021. We measured plasma biomarkers using single molecule array technology [ubiquitin C-terminal hydrolase L1 (UCH-L1), neurofilament light (NfL), tau, glial fibrillary acidic protein (GFAP) and phosphorylated tau (P-tau181)]; PET tracers to measure amyloid-\u03b2 (18F-NAV4694) and tau neurofibrillary tangles (18F-MK6240); MRI to assess white matter microstructure and brain age; and the Rey Auditory Verbal Learning Test to measure verbal-episodic memory.<\/jats:p>\n                  <jats:p>A total of 90 post-TBI participants (73% male; mean = 58.2 years) were recruited on average 22 years (range = 10\u201333 years) post-injury, and 32 non-TBI control participants (66% male; mean = 57.9 years) were recruited. Plasma UCH-L1 levels were 67% higher {exp(b) = 1.67, P = 0.018, adjusted P = 0.044, 95% confidence interval (CI) [10% to 155%], area under the curve = 0.616} and P-tau181 were 27% higher {exp(b) = 1.24, P = 0.011, adjusted P = 0.044, 95% CI [5% to 46%], area under the curve = 0.632} in TBI participants compared with controls. Amyloid and tau PET were not elevated in TBI participants. Higher concentrations of plasma P-tau181, UCH-L1, GFAP and NfL were significantly associated with worse white matter microstructure but not brain age in TBI participants. For TBI participants, poorer verbal-episodic memory was associated with higher concentration of P-tau181 {short delay: b = \u22122.17, SE = 1.06, P = 0.043, 95% CI [\u22124.28, \u22120.07]; long delay: bP-tau = \u22122.56, SE = 1.08, P = 0.020, 95% CI [\u22124.71, \u22120.41]}, tau {immediate memory: bTau = \u22126.22, SE = 2.47, P = 0.014, 95% CI [\u221211.14, \u22121.30]} and UCH-L1 {immediate memory: bUCH-L1 = \u22122.14, SE = 1.07, P = 0.048, 95% CI [\u22124.26, \u22120.01]}, but was not associated with functional outcome.<\/jats:p>\n                  <jats:p>Elevated plasma markers related to neuronal damage and accumulation of phosphorylated tau suggest the presence of ongoing neuropathology in the chronic phase following a single moderate\u2013severe TBI. Plasma biomarkers were associated with measures of microstructural brain disruption on MRI and disordered cognition, further highlighting their utility as potential objective tools to monitor evolving neuropathology post-TBI.<\/jats:p>","DOI":"10.1093\/brain\/awae255","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T04:18:00Z","timestamp":1721967480000},"page":"3690-3701","source":"Crossref","is-referenced-by-count":18,"title":["Plasma biomarkers in chronic single moderate\u2013severe traumatic brain injury"],"prefix":"10.1093","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7810-1480","authenticated-orcid":false,"given":"Gershon","family":"Spitz","sequence":"first","affiliation":[{"name":"Monash-Epworth Rehabilitation Research Centre, School of Psychological Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton, VIC 3800 ,","place":["Australia"]},{"name":"Department of Neuroscience, School of Translational Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1152-0576","authenticated-orcid":false,"given":"Amelia J","family":"Hicks","sequence":"additional","affiliation":[{"name":"Monash-Epworth Rehabilitation Research Centre, School of Psychological Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton, VIC 3800 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart J","family":"McDonald","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton, VIC 3004 ,","place":["Australia"]},{"name":"Department of Neurology, The Alfred , Melbourne, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Dore","sequence":"additional","affiliation":[{"name":"Florey Department of Neuroscience and Mental Health, University of Melbourne , Parkville, VIC 3010 ,","place":["Australia"]},{"name":"Department of Molecular Imaging and Therapy, Austin Health , Heidelberg, VIC 3084 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Krishnadas","sequence":"additional","affiliation":[{"name":"Florey Department of Neuroscience and Mental Health, University of Melbourne , Parkville, VIC 3010 ,","place":["Australia"]},{"name":"Department of Molecular Imaging and Therapy, Austin Health , Heidelberg, VIC 3084 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence J","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton, VIC 3004 ,","place":["Australia"]},{"name":"Department of Neurology, The Alfred , Melbourne, VIC 3004 ,","place":["Australia"]},{"name":"Department of Medicine, Royal Melbourne Hospital, The University of Melbourne , Parkville, VIC 3010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William T","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1182-0907","authenticated-orcid":false,"given":"Lucy","family":"Vivash","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton, VIC 3004 ,","place":["Australia"]},{"name":"Department of Neurology, The Alfred , Melbourne, VIC 3004 ,","place":["Australia"]},{"name":"Department of Medicine, Royal Melbourne Hospital, The University of Melbourne , Parkville, VIC 3010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Law","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton, VIC 3004 ,","place":["Australia"]},{"name":"Department of Radiology, Alfred Health , Melbourne, VIC 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennie L","family":"Ponsford","sequence":"additional","affiliation":[{"name":"Monash-Epworth Rehabilitation Research Centre, School of Psychological Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton, VIC 3800 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Rowe","sequence":"additional","affiliation":[{"name":"Florey Department of Neuroscience and Mental Health, University of Melbourne , Parkville, VIC 3010 ,","place":["Australia"]},{"name":"Department of Molecular Imaging and Therapy, Austin Health , Heidelberg, VIC 3084 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2525-8775","authenticated-orcid":false,"given":"Sandy R","family":"Shultz","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton, VIC 3004 ,","place":["Australia"]},{"name":"Department of Neurology, The Alfred , Melbourne, VIC 3004 ,","place":["Australia"]},{"name":"The Centre for Trauma and Mental Health Research, Health Sciences and Human Services, Vancouver Island University , Nanaimo, BC V9R 5S5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,9,24]]},"reference":[{"key":"2024110323584789800_awae255-B1","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/S1474-4422(17)30371-X","article-title":"Traumatic brain injury: Integrated approaches to improve prevention, clinical care, and research","volume":"16","author":"Maas","year":"2017","journal-title":"Lancet Neurol"},{"key":"2024110323584789800_awae255-B2","doi-asserted-by":"crossref","first-page":"eaaw1993","DOI":"10.1126\/scitranslmed.aaw1993","article-title":"In vivo detection of cerebral tau pathology in long-term survivors of traumatic brain injury","volume":"11","author":"Gorgoraptis","year":"2019","journal-title":"Sci Transl Med."},{"key":"2024110323584789800_awae255-B3","doi-asserted-by":"crossref","first-page":"eabg9922","DOI":"10.1126\/scitranslmed.abg9922","article-title":"Axonal 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