Serum tau fragments as predictors of death or poor neurological outcome after out-of-hospital cardiac arrest

Grand, Johannes; Kjærgaard, Jesper; Nielsen, Niklas; Friberg, Hans; Cronberg, Tobias; Bro-Jeppesen, John; Karsdal, Morten A.; Nielsen, Henning Bay; Frydland, Martin; Henriksen, Kim; Mattsson, Niklas; Zetterberg, Henrik; Hassager, Christian

doi:10.1080/1354750x.2019.1609580

Cited by 3 publications

(3 citation statements)

References 33 publications

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“…One possibility is that transport across the blood-brain-barrier differs between GFAP-C6 and full-length GFAP. This has been suggested to explain the lack of correlation between T-tau and two fragments of tau measured in serum obtained from the same CA cohort as applied in this study [50]. Another possibility is, that the cleavage of GFAP-C6 is a limiting factor in relation to how fast the fragment is generated.…”

Section: Discussionmentioning

confidence: 83%

“…The lack of correlation between GFAP-C6 and markers of injury, T-tau and NSE, is surprising. However, levels of the two other proteolytic fragments, tau-A and tau-C, did not correlate with T-tau or NSE, either [50]. In light of these findings, future studies on the correlation between GFAP-C6 and its full-length counterpart, GFAP, could provide interesting knowledge on the biology behind GFAP-C6 formation and release.…”

Section: Discussionmentioning

confidence: 99%

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A caspase-6-cleaved fragment of Glial Fibrillary Acidic Protein as a potential serological biomarker of CNS injury after cardiac arrest

et al. 2019

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Blood levels of Glial Fibrillary Acidic protein (GFAP) reflect processes associated with different types of CNS injury. Evidence suggests that GFAP is cleaved by caspases during CNS injury, hence positioning GFAP fragments as potential biomarkers of injury-associated processes. We set out to develop an assay detecting the neo-epitope generated by caspase-6 cleavage of GFAP (GFAP-C6), and to assess the ability of GFAP-C6 to reflect pathological processes in patients suffering a cardiac arrest and subsequent global cerebral ischemia. Anti-GFAP-C6 antibodies recognized their specific target sequence, and dilution and spike recoveries in serum were within limits of ±20% reflecting high precision and accuracy of measurements. Intra- and inter-assay CVs were below limits of 10% and 15%, respectively. Serological levels of GFAP-C6 were significantly elevated 72 hours after CA (Mean±SD) (20.39±10.59 ng/mL) compared to time of admission (17.79±10.77 ng/mL, p<0.0001), 24 hours (17.40±7.99 ng/mL, p<0.0001) and 48 hours (17.87±8.56 ng/mL, p<0.0001) after CA, but were not related to neurological outcome at day 180. GFAP-C6 levels at admission, 24, 48, and 72 hours after cardiac arrest correlated with two proteolytic fragments of tau, tau-A (r = 0.30, r = 0.40, r = 0.50, r = 0.53, p < 0.0001) and tau-C (r = 54, r = 0.48, r = 0.55, r = 0.54, p < 0.0001), respectively. GFAP-C6 levels did not correlate with other markers of CNS damage; total tau, NSE and S100B. In conclusion, we developed the first assay detecting a caspase-6 cleaved fragment of GFAP in blood. Increased levels at 72 hours after cardiac arrest as well as moderate correlations between GFAP-C6 and two other blood biomarkers of neurodegeneration suggest the ability of GFAP-C6 to reflect pathological processes of the injured brain. Investigations into the potential of GFAP-C6 in other types of CNS injury are warranted.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

A caspase-6-cleaved fragment of Glial Fibrillary Acidic Protein as a potential serological biomarker of CNS injury after cardiac arrest

et al. 2019

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“…The accuracy of serial serum Tau, a neuron-derived protein, at 24, 48, and 72 h after ROSC is comparable with serial serum NSE for predicting poor outcomes [62]. However, the role of serum Tau fragments, Tau-A and Tau-C, in cardiac arrest prognostication remains uncertain [63]. Serial plasma neurofilament light chain at 24, 48, and 72 h after ROSC with the respective cutoff value of 127, 263, and 344 pg/ml is predictive for poor outcomes [64].…”

Section: Other Biochemical Markersmentioning

confidence: 99%

Prognostication in Post-Cardiac Arrest Patients

Piyayotai¹,

Muengtaweepongsa²

2022

Cardiac Arrhythmias - Translational Approach From Pathophysiology to Advanced Care

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After resuscitation from cardiac arrest, a combination of the complex pathophysiologic process, known as post-cardiac arrest syndrome (PCAS), is attributed to multiple organ damage. Global ischemic cascade occurs in the brain due to generalized ischemia during cardiac arrest and the reperfusion process after the return of spontaneous circulation (ROSC), leading to hypoxic/ ischemic brain injury. Targeted temperature management (TTM) is a well-known neuroprotective therapy for ischemic/hypoxic brain injury. This global brain injury is a significant cause of death in PCAS. The implementation of TTM for PCAS leads to a reduction in mortality and better clinical outcomes among survivors. Prognostication is an essential part of post-resuscitation care. Before the TTM era, physicians relied on the algorithm for prognostication in comatose patients released by the American Academy of Neurology in 2006. However, TTM also announced more significant uncertainty during prognostication. During this TTM era, prognostication should not rely on just a solitary parameter. The trend of prognostication turns into a multimodal strategy integrating physical examination with supplementary methods, consisting of electrophysiology such as somatosensory evoked potential (SSEP) and electroencephalography (EEG), blood biomarkers, particularly serum neuron-specific enolase (NSE), and neuro-radiography including brain imaging with CT/MRI, to enhance prognostic accuracy.

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Serum tau as a predictor for neurological outcome after cardiopulmonary resuscitation

et al. 2020

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Serum tau fragments as predictors of death or poor neurological outcome after out-of-hospital cardiac arrest

Cited by 3 publications

References 33 publications

A caspase-6-cleaved fragment of Glial Fibrillary Acidic Protein as a potential serological biomarker of CNS injury after cardiac arrest

A caspase-6-cleaved fragment of Glial Fibrillary Acidic Protein as a potential serological biomarker of CNS injury after cardiac arrest

Prognostication in Post-Cardiac Arrest Patients

Serum tau as a predictor for neurological outcome after cardiopulmonary resuscitation

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