Comparing Glial Fibrillary Acidic Protein (GFAP) in Serum and Plasma Following Mild Traumatic Brain Injury in Older Adults

Huebschmann, Nathan A; Luoto, Teemu M.; Karr, Justin E; Berghem, Ksenia; Blennow, Kaj; Zetterberg, Henrik; Ashton, Nicholas J.; Simrén, Joel; Posti, Jussi P.; Gill, Jessica; Iverson, Grant L.

doi:10.3389/fneur.2020.01054

Cited by 53 publications

(39 citation statements)

References 47 publications

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“…It should also be considered that, in Verberk et al, GFAP was measured in serum, as opposed to plasma in the present study. So far, only one study has compared plasma and serum concentrations of GFAP in a traumatic brain injury cohort, with good correlation but significantly higher concentrations of GFAP in plasma [ 19 ]. Extensive head-to-head comparisons are yet to be done between the two different methods of analysis and it cannot be excluded that the presence of clotting agents in the sample might affect the results.…”

Section: Discussionmentioning

confidence: 99%

“…Glial fibrillary acidic protein (GFAP) is expressed in the cytoskeleton of astrocytes and has been found significantly increased in CSF in AD and other neurodegenerative diseases compared to healthy controls [12][13][14][15]. GFAP has also been recently measured in plasma and serum, where it was found increased in different neurological conditions, including AD [16][17][18][19][20][21][22][23][24]. Different studies have shown that higher concentrations of plasma GFAP were associated to amyloid-PET positivity and worse outcomes in global cognition [22,[24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

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Plasma glial fibrillary acidic protein detects Alzheimer pathology and predicts future conversion to Alzheimer dementia in patients with mild cognitive impairment

et al. 2021

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Introduction Plasma glial fibrillary acidic protein (GFAP) is a marker of astroglial activation and astrocytosis. We assessed the ability of plasma GFAP to detect Alzheimer’s disease (AD) pathology in the form of AD-related amyloid-β (Aβ) pathology and conversion to AD dementia in a mild cognitive impairment (MCI) cohort. Method One hundred sixty MCI patients were followed for 4.7 years (average). AD pathology was defined using cerebrospinal fluid (CSF) Aβ42/40 and Aβ42/total tau (T-tau). Plasma GFAP was measured at baseline and follow-up using Simoa technology. Results Baseline plasma GFAP could detect abnormal CSF Aβ42/40 and CSF Aβ42/T-tau with an AUC of 0.79 (95% CI 0.72–0.86) and 0.80 (95% CI 0.72–0.86), respectively. When also including APOE ε4 status as a predictor, the accuracy of the model to detect abnormal CSF Aβ42/40 status improved (AUC = 0.86, p = 0.02). Plasma GFAP predicted subsequent conversion to AD dementia with an AUC of 0.84 (95% CI 0.77–0.91), which was not significantly improved when adding APOE ε4 or age as predictors to the model. Longitudinal GFAP slopes for Aβ-positive and MCI who progressed to dementia (AD or other) were significantly steeper than those for Aβ-negative (p = 0.007) and stable MCI (p < 0.0001), respectively. Conclusion Plasma GFAP can detect AD pathology in patients with MCI and predict conversion to AD dementia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Plasma glial fibrillary acidic protein detects Alzheimer pathology and predicts future conversion to Alzheimer dementia in patients with mild cognitive impairment

et al. 2021

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“…In contrast, tau, is present in unmyelinated axons of neurons, but also in astrocytes and oligodendrocytes, which may explain why low serum concentrations indicate little or no injury (or astrocytic upregulation) [ 45 ]. All three markers are currently studied as prognostic markers within various neurological conditions and may soon become widely available [ 30 , 31 , 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest

Moseby-Knappe

Mattsson‐Carlgren

Stammet³

et al. 2021

Intensive Care Med

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Purpose The majority of unconscious patients after cardiac arrest (CA) do not fulfill guideline criteria for a likely poor outcome, their prognosis is considered “indeterminate”. We compared brain injury markers in blood for prediction of good outcome and for identifying false positive predictions of poor outcome as recommended by guidelines. Methods Retrospective analysis of prospectively collected serum samples at 24, 48 and 72 h post arrest within the Target Temperature Management after out-of-hospital cardiac arrest (TTM)-trial. Clinically available markers neuron-specific enolase (NSE) and S100B, and novel markers neurofilament light chain (NFL), total tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were analysed. Normal levels with a priori cutoffs specified by reference laboratories or defined from literature were used to predict good outcome (no to moderate disability, Cerebral Performance Category scale 1–2) at 6 months. Results Seven hundred and seventeen patients were included. Normal NFL, tau and GFAP had the highest sensitivities (97.2–98% of poor outcome patients had abnormal serum levels) and NPV (normal levels predicted good outcome in 87–95% of patients). Normal S100B and NSE predicted good outcome with NPV 76–82.2%. Normal NSE correctly identified 67/190 (35.3%) patients with good outcome among those classified as “indeterminate outcome” by guidelines. Five patients with single pathological prognostic findings despite normal biomarkers had good outcome. Conclusion Low levels of brain injury markers in blood are associated with good neurological outcome after CA. Incorporating biomarkers into neuroprognostication may help prevent premature withdrawal of life-sustaining therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06481-4.

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“…Glial brillary acidic protein (GFAP) is expressed in the cytoskeleton of astrocytes and has been found signi cantly increased in CSF in AD and other neurodegenerative diseases compared to healthy controls (12)(13)(14)(15). GFAP has also been recently measured in plasma and serum, where it was found increased in different neurological conditions, including AD (16)(17)(18)(19)(20)(21)(22)(23)(24). Increase of plasma GFAP in AD patients was associated to amyloid-PET positivity and worse outcomes in global cognition (22,24,25).…”

Section: Introductionmentioning

confidence: 99%

Plasma Glial Fibrillary Acidic Protein Detects Alzheimer Pathology and Predicts Future Conversion to Alzheimer Dementia in Patients With Mild Cognitive Impairment

Cicognola¹,

Bateman²,

Hertze

et al. 2020

Preprint

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IntroductionPlasma glial fibrillary acidic protein (GFAP) is a marker of astroglial activation and astrocytosis. We assessed the ability of plasma GFAP to detect Alzheimer’s disease (AD) pathology in the form of AD-related amyloid-b (Aβ) pathology and conversion to AD dementia in a mild cognitive impairment (MCI) cohort.Method160 MCI patients were followed for 4.7 years (average). AD pathology was defined using cerebrospinal fluid (CSF) Aβ42/40 and Aβ42/total tau. Plasma GFAP was measured at baseline and follow-up using Simoa technology.ResultsBaseline plasma GFAP could detect abnormal CSF Aβ42/40 and CSF Aβ42/total tau (T-tau) with an AUC of 0.79 (95% CI 0.72-0.86) and 0.80 (95% CI 0.72-0.86), respectively. Combination with APOE ε4 status improved the diagnostic accuracy for abnormal CSF Aβ42/40 status (AUC=0.86, p=0.02). Plasma GFAP predicted subsequent conversion to AD dementia with an AUC of 0.84 (95% CI 0.77-0.91), which was not significantly improved when combined with APOE ε4 or age. Longitudinal GFAP slopes for Aβ-positive and MCI who progressed to AD dementia were significantly steeper than for Aβ-negative (p=0.007) and stable MCI (p<0.0001).ConclusionPlasma GFAP can detect AD pathology in patients with MCI and predict conversion to AD dementia.

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Comparing Glial Fibrillary Acidic Protein (GFAP) in Serum and Plasma Following Mild Traumatic Brain Injury in Older Adults

Cited by 53 publications

References 47 publications

Plasma glial fibrillary acidic protein detects Alzheimer pathology and predicts future conversion to Alzheimer dementia in patients with mild cognitive impairment

Plasma glial fibrillary acidic protein detects Alzheimer pathology and predicts future conversion to Alzheimer dementia in patients with mild cognitive impairment

Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest

Plasma Glial Fibrillary Acidic Protein Detects Alzheimer Pathology and Predicts Future Conversion to Alzheimer Dementia in Patients With Mild Cognitive Impairment

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