Accuracy of a rapid glial fibrillary acidic protein/ubiquitin carboxyl‐terminal hydrolase L1 test for the prediction of intracranial injuries on head computed tomography after mild traumatic brain injury

Welch, Robert D.; Caudle, Krista L.; Jeffrey, Craig A.; Chen, James Y.; Chandran, Raj; McCaw, Tamara; Datwyler, Saul A.; Zhang, Hongwei; McQuiston, Beth

doi:10.1111/acem.14366

Cited by 41 publications

(25 citation statements)

References 37 publications

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“…It was suggested that GFAP levels in plasma reflect amyloid-b pathology better than CSF levels as only plasma GFAP could differentiate between amyloid-b positive and negative CN individuals 15 . However, it is also clear that increased plasma GFAP may not only be present in AD, as astrocytosis occurs in response to many different pathological processes in the CNS 46 , and increased plasma GFAP levels have also been linked with conditions such as traumatic brain injury, stroke, FTD, and multiple sclerosis 44,[47][48][49] . It remains to be determined how plasma GFAP can be utilized in AD, but it can be speculated that its early and gradual increase together with its association with amyloid-b pathology would make it useful for predicting and following disease progression both in clinical practice and during clinical trials, as well as to support inclusion of individuals with early AD 50 .…”

Section: Discussionmentioning

confidence: 99%

Plasma biomarkers for diagnosis of Alzheimer’s disease and prediction of cognitive decline in individuals with mild cognitive impairment

Kivisäkk

Sweeney

Carlyle

et al. 2022

Preprint

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Background: The last few years have seen major advances in blood biomarkers for Alzheimer's Disease (AD) with the development of ultrasensitive immunoassays, promising to transform how we diagnose, prognose, and track progression of neurodegenerative dementias. Methods: We evaluated a panel of four novel ultrasensitive electrochemiluminescence (ECL) immunoassays against presumed CNS derived proteins of interest in AD in plasma [phosphorylated-Tau181 (pTau181), total Tau (tTau), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP)]. 366 plasma samples from the Massachusetts Alzheimer's Disease Research Center's longitudinal cohort study were examined to differentiate definite AD, other neurodegenerative diseases (OND), and cognitively normal (CN) individuals. A subset of samples were selected to have longitudinal follow up to also determine the utility of this plasma biomarker panel in predicting 4-year risk for cognitive decline in individuals with different levels of cognitive impairment. Results: pTau181, tTau and GFAP were higher in AD compared to CN and OND, while NfL was elevated in AD and further increased in OND. pTau181 performed the best (AD vs CN: AUC=0.88, 2-fold increase; AD vs OND: AUC=0.78, 1.5-fold increase) but tTau also showed excellent discrimination (AD vs CN: AUC=0.79, 1.5-fold increase; AD vs OND: AUC=0.72, 1.3-fold increase). Participants with MCI who progressed to AD dementia had higher baseline plasma concentrations of pTau181, NfL, and GFAP compared to non-progressors with the best discrimination for pTau181 (AUC=0.82, 1.7-fold increase) and GFAP (AUC=0.81, 1.6-fold increase). Conclusions: These new ultrasensitive ECL plasma assays for pTau181, tTau, NfL, and GFAP detect CNS disease with high specificity and accuracy. Moreover, the absolute baseline plasma levels of pTau and GFAP reflect clinical disease aggressiveness over the next 4 years, providing diagnostic and prognostic information that may have utility in both clinical and clinical trial populations. Classification of Evidence: This study provides Class II evidence that plasma levels of pTau181, tTau, NfL, and GFAP are associated with AD and that pTau181 and GFAP are associated with progression from MCI to AD dementia.

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Section: Discussionmentioning

confidence: 99%

Plasma biomarkers for diagnosis of Alzheimer’s disease and prediction of cognitive decline in individuals with mild cognitive impairment

Kivisäkk

Sweeney

Carlyle

et al. 2022

Preprint

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“…Recently, the company Abbott Laboratories (Chicago, IL USA) has developed the FDA approved Abbott's i-STAT™ Alinity™ handheld device which can produce UCHL1 results within 15 min after a plasma sample has been inserted. This technology has been shown to have good sensitivity in predicting acute traumatic intracranial injury 14 . All these advancements make the investigation of UCHL1 as a biomarker that may aid in SRC diagnosis quite lucrative.…”

Section: Introductionmentioning

confidence: 99%

Ubiquitin carboxyl-terminal esterase L1 is not elevated in the serum of concussed rugby players: an observational cross-sectional study

Harrell

Morgan

Beck

et al. 2022

Sci Rep

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Concussion diagnosis is complicated by a lack of objective measures. Ubiquitin carboxyl-terminal esterase L1 (UCHL1) is a biomarker that has been shown to increase following traumatic brain injury but has not been investigated in concussed athletes on the sideline of athletic events. Therefore, this study was conducted to determine if UCHL1 can be used to aid in sideline concussion diagnosis. Blood was taken via standard venipuncture from a recreationally active control group, a group of rugby players prior to match play (pre-match), rugby players following match-play (match-control), and rugby players after suffering a sport-related concussion (SRC). UCHL1 was not significantly different among groups (p > 0.05) and was unable to distinguish between SRC and controls (AUROC < 0.400, p > 0.05). However, when sex-matched data were used, it was found that the female match-control group had a significantly higher serum UCHL1 concentration than the pre-match group (p = 0.041). Differences were also found in serum UCHL1 concentrations between male and female athletes in the match-control group (p = 0.007). This study does not provide evidence supporting the use of UCHL1 in sideline concussion diagnosis when blood is collected soon after concussion but does show differences in serum UCHL1 accumulation between males and females.

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“…However, many of these features, notably PTA, typically rely on subjective self-report. Recently, the blood-based biomarker, GFAP (a marker of astrocytic response to injury), has been identified as having clinical utility in evaluation of mTBI [ 16 ], a diagnosis which historically has also relied upon subjective symptom reporting and clinical judgement. It is therefore plausible that blood-based biomarkers could similarly be used to predict post-TBI mental health outcomes such as PTSD.…”

Section: Discussionmentioning

confidence: 99%

“…Banyan Biomarkers; 2018; i-STAT TBI Plasma Cartridge. Abbott Point of Care Inc. Abbott Park, IL; 2020) [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Association of day-of-injury plasma glial fibrillary acidic protein concentration and six-month posttraumatic stress disorder in patients with mild traumatic brain injury

Kulbe

Jain

Nelson

et al. 2022

Neuropsychopharmacol.

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Several proteins have proven useful as blood-based biomarkers to assist in evaluation and management of traumatic brain injury (TBI). The objective of this study was to determine whether two day-of-injury blood-based biomarkers are predictive of posttraumatic stress disorder (PTSD). We used data from 1143 individuals with mild TBI (mTBI; defined as admission Glasgow Coma Scale [GCS] score 13–15) enrolled in TRACK-TBI, a prospective longitudinal study of level 1 trauma center patients. Plasma glial fibrillary acidic protein (GFAP) and high sensitivity C-reactive protein (hsCRP) were measured from blood collected within 24 h of injury. Two hundred and twenty-seven (19.9% of) patients had probable PTSD (PCL-5 score ≥ 33) at 6 months post-injury. Serum GFAP levels were positively associated (Spearman’s rho = 0.35, p < 0.001) with duration of posttraumatic amnesia (PTA). There was an inverse association between PTSD and (log)GFAP (adjusted OR = 0.85, 95% CI 0.77–0.95 per log unit increase) levels, but no significant association with (log)hsCRP (adjusted OR = 1.11, 95% CI 0.98–1.25 per log unit increase) levels. Elevated day-of-injury serum GFAP, a biomarker of glial reactivity, is associated with reduced risk of PTSD after mTBI. This finding merits replication and additional studies to determine a possible neurocognitive basis for this relationship.

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Accuracy of a rapid glial fibrillary acidic protein/ubiquitin carboxyl‐terminal hydrolase L1 test for the prediction of intracranial injuries on head computed tomography after mild traumatic brain injury

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 41 publications

References 37 publications

Plasma biomarkers for diagnosis of Alzheimer’s disease and prediction of cognitive decline in individuals with mild cognitive impairment

Plasma biomarkers for diagnosis of Alzheimer’s disease and prediction of cognitive decline in individuals with mild cognitive impairment

Ubiquitin carboxyl-terminal esterase L1 is not elevated in the serum of concussed rugby players: an observational cross-sectional study

Association of day-of-injury plasma glial fibrillary acidic protein concentration and six-month posttraumatic stress disorder in patients with mild traumatic brain injury

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