Kimbra Kenney1,2, Bao-Xi Qu1, Chen Lai3, Christina Devoto3, Vida Motamedi3, William C Walker4, Harvey S Levin5,6, Tracy Nolen7, Elisabeth A Wilde5,6,8, Ramon Diaz-Arrastia9, Jessica Gill3,10. 1. a Department of Neurology , Uniformed Services University of the Health Sciences , Bethesda , MD , USA. 2. b National Intrepid Center of Excellence , Walter Reed National Military Medical Center , Bethesda , MD , USA. 3. c National Institutes of Health , National Institute of Nursing Research , Bethesda , MD , USA. 4. d Department of Physical Medicine & Rehabilitation , Virginia Commonwealth University , Richmond , VA , USA. 5. e Department of Physical Medicine and Rehabilitation , Baylor College of Medicine , Houston , TX , USA. 6. f VA Rehabilitation Research Center of Excellence , Michael E DeBakey VA Medical Center , Houston , TX , USA. 7. g RTI International , Research Triangle Park NC , USA. 8. h Department of Neurology , University of Utah School of Medicine , Salt Lake City , UT , USA. 9. i Department of Neurology , University of Pennsylvania , Philadelphia , PA , USA. 10. j Center for Neuroscience and Regenerative Medicine, Biomarker Core , Uniformed Services University of the Health Sciences , Bethesda , MD , USA.
Abstract
OBJECTIVE: The objective of the study is to measure plasma and exosomal levels of tau, phosphorylated tau (p-tau), and amyloid beta (Aβ) in Veterans with historical mild traumatic brain injury (mTBI) and chronic neuropsychological symptoms. METHODS: Tau, p-tau, Aβ40, and Aβ42 were measured by ultrasensitive immunoassay in plasma and exosomes from 195 Veterans enrolled in the Chronic Effects of Neurotrauma Consortium Multicenter Observational Study. Protein biomarkers were compared among groups with and without mTBI with loss of consciousness (LOC) or post-traumatic amnesia (PTA), and also in those with and without repetitive (≥3) mTBI (rTBI) compared to those with 0 (TBI-neg) and 1-2 mTBI. RESULTS: There were no differences in measures of plasma and exosomal protein levels among mTBI with LOC or PTA, mTBI with alteration of consciousness only or TBI-neg. Exosomal tau and exosomal p-tau were elevated in rTBI compared to those with 2 or fewer mTBIs and TBI-neg (p < 0.05). Elevations of exosomal tau and p-tau significantly correlated with post-traumatic and post-concussive symptoms, with exosomal tau also relating specifically to cognitive, affective, and somatic post-concussive symptoms (p < 0.05). CONCLUSION: rTBI is associated with elevations of exosomal p-tau and exosomal tau, suggesting that blood-based exosomes may provide a peripheral source of informative, centrally derived biomarkers in remote mTBI and that rTBI may contribute to chronic neuropsychological symptoms.
OBJECTIVE: The objective of the study is to measure plasma and exosomal levels of tau, phosphorylated tau (p-tau), and amyloid beta (Aβ) in Veterans with historical mild traumatic brain injury (mTBI) and chronic neuropsychological symptoms. METHODS: Tau, p-tau, Aβ40, and Aβ42 were measured by ultrasensitive immunoassay in plasma and exosomes from 195 Veterans enrolled in the Chronic Effects of Neurotrauma Consortium Multicenter Observational Study. Protein biomarkers were compared among groups with and without mTBI with loss of consciousness (LOC) or post-traumatic amnesia (PTA), and also in those with and without repetitive (≥3) mTBI (rTBI) compared to those with 0 (TBI-neg) and 1-2 mTBI. RESULTS: There were no differences in measures of plasma and exosomal protein levels among mTBI with LOC or PTA, mTBI with alteration of consciousness only or TBI-neg. Exosomal tau and exosomal p-tau were elevated in rTBI compared to those with 2 or fewer mTBIs and TBI-neg (p < 0.05). Elevations of exosomal tau and p-tau significantly correlated with post-traumatic and post-concussive symptoms, with exosomal tau also relating specifically to cognitive, affective, and somatic post-concussive symptoms (p < 0.05). CONCLUSION: rTBI is associated with elevations of exosomal p-tau and exosomal tau, suggesting that blood-based exosomes may provide a peripheral source of informative, centrally derived biomarkers in remote mTBI and that rTBI may contribute to chronic neuropsychological symptoms.
Authors: Sara M Lippa; Ping-Hong Yeh; Jessica Gill; Louis M French; Tracey A Brickell; Rael T Lange Journal: J Neurotrauma Date: 2019-04-09 Impact factor: 5.269
Authors: Vladislav Bugay; Eda Bozdemir; Fabio A Vigil; Sang H Chun; Deborah M Holstein; William R Elliott; Cassie J Sprague; Jose E Cavazos; David O Zamora; Gregory Rule; Mark S Shapiro; James D Lechleiter; Robert Brenner Journal: J Neurotrauma Date: 2019-10-21 Impact factor: 5.269
Authors: David F Tate; Emily L Dennis; John T Adams; Maheen M Adamson; Heather G Belanger; Erin D Bigler; Heather C Bouchard; Alexandra L Clark; Lisa M Delano-Wood; Seth G Disner; Blessen C Eapen; Carol E Franz; Elbert Geuze; Naomi J Goodrich-Hunsaker; Kihwan Han; Jasmeet P Hayes; Sidney R Hinds; Cooper B Hodges; Elizabeth S Hovenden; Andrei Irimia; Kimbra Kenney; Inga K Koerte; William S Kremen; Harvey S Levin; Hannah M Lindsey; Rajendra A Morey; Mary R Newsome; John Ollinger; Mary Jo Pugh; Randall S Scheibel; Martha E Shenton; Danielle R Sullivan; Brian A Taylor; Maya Troyanskaya; Carmen Velez; Benjamin Sc Wade; Xin Wang; Ashley L Ware; Ross Zafonte; Paul M Thompson; Elisabeth A Wilde Journal: Brain Imaging Behav Date: 2021-01-07 Impact factor: 3.978
Authors: James S Meabon; David G Cook; Mayumi Yagi; Garth E Terry; Donna J Cross; Mark Muzi; Kathleen F Pagulayan; Aric F Logsdon; Abigail G Schindler; Vikas Ghai; Kai Wang; Shannon Fallen; Yong Zhou; Taek-Kyun Kim; Inyoul Lee; William A Banks; Erik S Carlson; Cynthia Mayer; Rebecca C Hendrickson; Murray A Raskind; Desiree A Marshall; Daniel P Perl; C Dirk Keene; Elaine R Peskind Journal: J Neurol Sci Date: 2020-07-18 Impact factor: 3.181