Elevated Tau in Military Personnel Relates to Chronic Symptoms Following Traumatic Brain Injury

Pattinson, C.; Shahim, Pashtun; Taylor, Patricia; Dunbar, Kerri; Guedes, Vivian A.; Motamedi, Vida; Lai, Chen; Devoto, Christina; Peyer, Jordan; Roy, Michael J.; Gill, Jessica

doi:10.1097/htr.0000000000000485

Cited by 33 publications

(37 citation statements)

References 54 publications

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“… 7 , 25 , 28 Indeed, our laboratory has previously observed that plasma Nf-L concentrations were elevated in military personnel who had sustained repetitive TBIs compared with those with 1 or 2 TBIs, but no differences were observed between control and TBI groups. 29 Despite recent progress in SRCs, the prognostic value of Nf-L is yet to be fully ascertained. We hypothesize that Nf-L has limited sensitivity in milder cases of SRC and may become more evident as the number of SRCs sustained increases.…”

Section: Discussionmentioning

confidence: 99%

Plasma Biomarker Concentrations Associated With Return to Sport Following Sport-Related Concussion in Collegiate Athletes—A Concussion Assessment, Research, and Education (CARE) Consortium Study

et al. 2020

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Key Points Question Are plasma biomarkers associated with a return-to-sport period of less than 14 days vs 14 days or more in male and female collegiate athletes following a sport-related concussion? Findings This diagnostic study, which included 127 collegiate athletes who had sustained a sports-related concussion, found that higher total tau concentrations 24 to 48 hours after injury and at the time of symptom resolution as well as lower glial fibrillary acidic protein levels acutely postinjury were associated with return-to-sport decisions. Meaning In this study, total tau and glial fibrillary acidic protein levels were associated with return to sport in male and female collegiate athletes following a sports-related concussion.

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Section: Discussionmentioning

confidence: 99%

Plasma Biomarker Concentrations Associated With Return to Sport Following Sport-Related Concussion in Collegiate Athletes—A Concussion Assessment, Research, and Education (CARE) Consortium Study

et al. 2020

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“…Biomarker studies in TBI have focused on plasma and serum levels of proteins found in brain cells such as tau, p-tau, and neurofilament light chain (NfL) ( 152 , 153 ); glial fibrillary acidic protein (GFAP), that is released from astrocytes ( 13 ); and ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1), a brain-specific deubiquitinating enzyme ( 154 ). NfL, GFAP, tau and UCHL1 have been linked to TBI severity, poor recovery, as well as PCS and PTSD symptomology in a variety of populations, including civilians ( 23 , 155 , 156 ), athletes ( 157 , 158 ) and military personnel ( 11 , 90 , 159 ). Other studies have evaluated levels of inflammatory markers ( 134 – 137 ) as previously discussed in this article.…”

Section: Extracellular Vesicles In Tbimentioning

confidence: 99%

“…Lifestyle, sex, genetic, and social factors, medical history, including previous head injuries, are all likely important determinants in TBI recovery (7,9). Indeed, sustaining multiple TBIs has been linked to lasting or worsening neurobehavioral symptoms, placing populations such as service members and contactsport athletes at a higher risk for worse outcomes following a TBI (10)(11)(12). The heterogeneous nature of TBI and limited understanding of underlying pathology represents a challenge to the development of effective therapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicle Proteins and MicroRNAs as Biomarkers for Traumatic Brain Injury

et al. 2020

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Traumatic brain injury (TBI) is a heterogeneous condition, associated with diverse etiologies, clinical presentations and degrees of severity, and may result in chronic neurobehavioral sequelae. The field of TBI biomarkers is rapidly evolving to address the many facets of TBI pathology and improve its clinical management. Recent years have witnessed a marked increase in the number of publications and interest in the role of extracellular vesicles (EVs), which include exosomes, cell signaling, immune responses, and as biomarkers in a number of pathologies. Exosomes have a well-defined lipid bilayer with surface markers that reflect the cell of origin and an aqueous core that contains a variety of biological material including proteins (e.g., cytokines and growth factors) and nucleic acids (e.g., microRNAs). The presence of proteins associated with neurodegenerative changes such as amyloid-β, α-synuclein and phosphorylated tau in exosomes suggests a role in the initiation and propagation of neurological diseases. However, mechanisms of cell communication involving exosomes in the brain and their role in TBI pathology are poorly understood. Exosomes are promising TBI biomarkers as they can cross the blood-brain barrier and can be isolated from peripheral fluids, including serum, saliva, sweat, and urine. Exosomal content is protected from enzymatic degradation by exosome membranes and reflects the internal environment of their cell of origin, offering insights into tissue-specific pathological processes. Challenges in the clinical use of exosomal cargo as biomarkers include difficulty in isolating pure exosomes, variable yields of the isolation processes, quantification of vesicles, and lack of specificity of exosomal markers. Moreover, there is no consensus regarding nomenclature and characteristics of EV subtypes. In this review, we discuss current technical limitations and challenges of using exosomes and other EVs as blood-based biomarkers, highlighting their potential as diagnostic and prognostic tools in TBI.

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“…Blood biomarkers have been investigated as predictors of neuroimaging abnormalities (abnormal CT and MRI scans) (9,20,(35)(36)(37)(38). Blood biomarkers have uncertain value in predicting the late effects of TBI (39)(40)(41)(42), in detecting sub-concussive blows to the head (43)(44)(45)(46), and in predicting readiness for return to play (47). Questions remain as to the preferred time to measure blood biomarkers, the preferred and Tmax are mid-range estimates † S100B is eliminated by first order kinetics.…”

Section: Introductionmentioning

confidence: 99%

A Kinetic Model for Blood Biomarker Levels After Mild Traumatic Brain Injury

et al. 2021

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Traumatic brain injury (TBI) imposes a significant economic and social burden. The diagnosis and prognosis of mild TBI, also called concussion, is challenging. Concussions are common among contact sport athletes. After a blow to the head, it is often difficult to determine who has had a concussion, who should be withheld from play, if a concussed athlete is ready to return to the field, and which concussed athlete will develop a post-concussion syndrome. Biomarkers can be detected in the cerebrospinal fluid and blood after traumatic brain injury and their levels may have prognostic value. Despite significant investigation, questions remain as to the trajectories of blood biomarker levels over time after mild TBI. Modeling the kinetic behavior of these biomarkers could be informative. We propose a one-compartment kinetic model for S100B, UCH-L1, NF-L, GFAP, and tau biomarker levels after mild TBI based on accepted pharmacokinetic models for oral drug absorption. We approximated model parameters using previously published studies. Since parameter estimates were approximate, we did uncertainty and sensitivity analyses. Using estimated kinetic parameters for each biomarker, we applied the model to an available post-concussion biomarker dataset of UCH-L1, GFAP, tau, and NF-L biomarkers levels. We have demonstrated the feasibility of modeling blood biomarker levels after mild TBI with a one compartment kinetic model. More work is needed to better establish model parameters and to understand the implications of the model for diagnostic use of these blood biomarkers for mild TBI.

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Elevated Tau in Military Personnel Relates to Chronic Symptoms Following Traumatic Brain Injury

Abstract: Objective: To understand the relationships between traumatic brain injury (TBI), blood biomarkers, and symptoms of posttraumatic stress disorder (PTSD), depression, and postconcussive syndrome symptoms (PCS).

Cited by 33 publications

References 54 publications

Plasma Biomarker Concentrations Associated With Return to Sport Following Sport-Related Concussion in Collegiate Athletes—A Concussion Assessment, Research, and Education (CARE) Consortium Study

Plasma Biomarker Concentrations Associated With Return to Sport Following Sport-Related Concussion in Collegiate Athletes—A Concussion Assessment, Research, and Education (CARE) Consortium Study

Extracellular Vesicle Proteins and MicroRNAs as Biomarkers for Traumatic Brain Injury

A Kinetic Model for Blood Biomarker Levels After Mild Traumatic Brain Injury

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