Detection of Glial Fibrillary Acidic Protein in Patient Plasma Using On-Chip Graphene Field-Effect Biosensors, in Comparison with ELISA and Single-Molecule Array

Background: Cerebrospinal fluid (CSF) levels of two soluble biomarkers, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL), have been shown to associate with multiple sclerosis (MS) disease progression. Now, both biomarkers can be detected reliably in serum, and importantly, their serum levels correlate well with their CSF levels. Objective: To evaluate the usability of serum GFAP measurement as a biomarker of progressive disease and disease severity in MS. Methods: Clinical course, Expanded Disability Status Scale (EDSS), disease duration, patient age and magnetic resonance imaging (MRI) parameters were reviewed in 79 MS patients in this cross-sectional hospital-based study. Serum samples were collected for measurement of GFAP and NfL concentrations using single molecule array (Simoa) assay. A cohort of healthy controls was evaluated for comparison. Results: Higher serum concentrations of both GFAP and NfL were associated with higher EDSS, older age, longer disease duration, progressive disease course and MRI pathology. Conclusion: Earlier studies have demonstrated that GFAP, unlike NfL, is not increased in association with acute focal inflammation-related nervous system damage. Our work suggests that GFAP serum level associates with disease progression in MS and could potentially serve as an easily measurable biomarker of central nervous system (CNS) pathology related to disease progression in MS.

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Glial-fibrillary-acidic-protein (GFAP) biomarker detection in serum-matrix: Functionalization strategies and detection by an ultra-high-frequency surface-acoustic-wave (UHF-SAW) lab-on-chip.

Biosensors and Bioelectronics ◽

10.1016/j.bios.2020.112774 ◽

2021 ◽

Vol 172 ◽

pp. 112774

Author(s):

M. Agostini ◽

F. Amato ◽

M.L. Vieri ◽

G. Greco ◽

I. Tonazzini ◽

...

Keyword(s):

Glial Fibrillary Acidic Protein ◽

Acoustic Wave ◽

Surface Acoustic Wave ◽

High Frequency ◽

Acidic Protein ◽

Biomarker Detection ◽

Lab On Chip ◽

Ultra High Frequency ◽

On Chip

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Absence of attack-independent neuroaxonal injury in MOG antibody-associated disease: Longitudinal assessment of serum neurofilament light chain

Multiple Sclerosis Journal ◽

10.1177/13524585211063756 ◽

2021 ◽

pp. 135245852110637

Author(s):

Jae-Won Hyun ◽

So Yeon Kim ◽

Yeseul Kim ◽

Na Young Park ◽

Ki Hoon Kim ◽

...

Keyword(s):

Glial Fibrillary Acidic Protein ◽

Single Molecule ◽

Light Chain ◽

Myelin Oligodendrocyte Glycoprotein ◽

Acidic Protein ◽

Healthy Controls ◽

Longitudinal Assessment ◽

Neurofilament Light Chain ◽

Neurofilament Light

To evaluate the occurrence of attack-independent neuroaxonal and astrocytic damage in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) levels were longitudinally measured in 102 sera using a single-molecule array assay. Sera from 15 adults with relapsing MOGAD with available longitudinal samples for the median 24-month follow-up and 26 age-/sex-matched healthy controls were analyzed. sNfL levels were significantly elevated in all clinical attacks, where the levels decreased below or close to cut-off value within 6 months after attacks. sNfL levels were consistently low during inter-attack periods. In contrast, sGFAP levels did not increase in most clinical attacks and remained low during follow-up. Significant neuroaxonal damage was observed at clinical attacks, while attack-independent neuroaxonal and astrocytic injury was absent in MOGAD.

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Serum Glial Fibrillary Acidic Protein (GFAP) Is a Marker of Disease Severity in Frontotemporal Lobar Degeneration

Journal of Alzheimer s Disease ◽

10.3233/jad-200608 ◽

2020 ◽

Vol 77 (3) ◽

pp. 1129-1141 ◽

Cited By ~ 1

Author(s):

Alberto Benussi ◽

Nicholas J. Ashton ◽

Thomas K. Karikari ◽

Stefano Gazzina ◽

Enrico Premi ◽

...

Keyword(s):

Glial Fibrillary Acidic Protein ◽

Disease Severity ◽

Single Molecule ◽

Frontotemporal Lobar Degeneration ◽

Acidic Protein ◽

Cross Sectional ◽

Indirect Measures ◽

Neurophysiological Data ◽

Diagnostic And Prognostic Value

Background: It is still unknown if serum glial fibrillary acidic protein (GFAP) is a useful marker in frontotemporal lobar degeneration (FTLD). Objective: To assess the diagnostic and prognostic value of serum GFAP in a large cohort of patients with FTLD. Methods: In this retrospective study, performed on 406 participants, we measured serum GFAP concentration with an ultrasensitive Single molecule array (Simoa) method in patients with FTLD, Alzheimer’s disease (AD), and in cognitively unimpaired elderly controls. We assessed the role of GFAP as marker of disease severity by analyzing the correlation with clinical variables, neurophysiological data, and cross-sectional brain imaging. Moreover, we evaluated the role of serum GFAP as a prognostic marker of disease survival. Results: We observed significantly higher levels of serum GFAP in patients with FTLD syndromes, except progressive supranuclear palsy, compared with healthy controls, but not compared with AD patients. In FTLD, serum GFAP levels correlated with measures of cognitive dysfunction and disease severity, and were associated with indirect measures of GABAergic deficit. Serum GFAP concentration was not a significant predictor of survival. Conclusion: Serum GFAP is increased in FTLD, correlates with cognition and GABAergic deficits, and thus shows promise as a biomarker of disease severity in FTLD.

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Plasma Glial Fibrillary Acidic Protein and Neurofilament-Light for the Diagnostic and Prognostic Evaluation of Frontotemporal Dementia

10.21203/rs.3.rs-958956/v1 ◽

2021 ◽

Author(s):

Nuole Zhu ◽

Miguel Santos-Santos ◽

Ignacio Illán-Gala ◽

Victor Montal ◽

Teresa Estellés ◽

...

Keyword(s):

Glial Fibrillary Acidic Protein ◽

Cognitive Decline ◽

Frontotemporal Dementia ◽

Cortical Thickness ◽

Single Molecule ◽

Diagnostic Performance ◽

Cognitive Outcome ◽

Acidic Protein ◽

Csf Biomarkers

Abstract Background: Astrocytes play an essential role in neuroinflammation and are involved in the pathogenesis of neurodenegerative diseases. The Study of Glial fibrillary acidic protein (GFAP), an astrocytic damage marker, may be helpful to better understand the different neurodegenerative diseases. We investigated the diagnostic performance of plasma GFAP (pGFAP), plasma neurofilament (pNfL) and their combination in frontotemporal dementia (FTD) and Alzheimer’s disease (AD). We studied their clinical utility in predicting disease progression. Methods: We measured pGFAP and pNfL concentrations in 72 FTD, 56 AD and 83 cognitively normal participants (CN) using Single Molecule Array technology. Of 211 participants, 199 had CSF and 122 had MRI. We compared cross-sectional biomarker levels between groups, studied their diagnostic performance and assessed correlation with CSF biomarkers, cognitive performance and cortical thickness. The prognostic performance was investigated analyzing cognitive decline between group comparisons by tertile. Results: Unlike pNfL, which was increased similarly in both clinical groups, pGFAP was increased in FTD but lower than in AD (all p<0.01). The combination of both plasma markers improved the diagnostic performance to discriminate FTD from AD (combination AUC 0.78; pGFAP AUC 0.7; pNfL AUC 0.61, all p<0.05). In FTD, pGFAP correlated with cognition, CSF and plasma NfL, and cortical thickness (all p<0.05). The higher tertile of pGFAP was associated with greater change in MMSE score and poor cognitive outcome during follow-up both in FTD (1.40 points annually, HR 3.82, p<0.005) and AD (1.20 points annually, HR 2.26, p<0.005).Conclusions: pGFAP and pNfL differed in FTD and AD, their combination could be useful to distinguish the two diseases. pGFAP could also be used to track disease severity and predict greater cognitive decline during follow-up in patients with FTD.

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Glial fibrillary acidic protein elevations relate to neuroimaging abnormalities after mild TBI

Neurology ◽

10.1212/wnl.0000000000006321 ◽

2018 ◽

Vol 91 (15) ◽

pp. e1385-e1389 ◽

Cited By ~ 34

Author(s):

Jessica Gill ◽

Lawrence Latour ◽

Ramon Diaz-Arrastia ◽

Vida Motamedi ◽

Christine Turtzo ◽

...

Keyword(s):

Brain Injury ◽

Glial Fibrillary Acidic Protein ◽

Single Molecule ◽

Brain Injuries ◽

Plasma Concentrations ◽

Acidic Protein ◽

Discriminatory Power ◽

Medical Decision ◽

Blood Concentrations ◽

Ct And Mri

ObjectivesTo determine whether a panel of blood-based biomarkers can discriminate between patients with suspected mild traumatic brain injury (mTBI) with and without neuroimaging findings (CT and MRI).MethodsStudy participants presented to the emergency department with suspected mTBI (n = 277) with a CT and MRI scan and healthy controls (n = 49). Plasma concentrations of tau, glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1, and neurofilament light chain (NFL) were measured using the single-molecule array technology.ResultsConcentrations of GFAP, tau, and NFL were higher in patients with mTBI, compared with those of controls (p's < 0.01). GFAP yielded an area under the curve (AUC) of 0.93 (95% confidence interval [CI] 0.90–0.96), confirming its discriminatory power for distinguishing mTBI from controls. Levels of GFAP, tau, and NFL were higher in patients with trauma-related intracranial findings on CT compared with those with normal CT, with the only significant predictor being GFAP (AUC 0.77, 95% CI 0.70–0.84). Among patients with mTBI, tau, NFL, and GFAP differentiated subjects with and without MRI abnormalities with an AUC of 0.83, with GFAP being the strongest predictor. Combining tau, NFL, and GFAP showed a good discriminatory power (AUC 0.80, 95% CI 0.69–0.90) for detecting MRI abnormalities, even in patients with mTBI with a normal CT.ConclusionOur study confirms GFAP as a promising marker of brain injury in patients with acute mTBI. A combination of various biomarkers linked to different pathophysiologic mechanisms increases diagnostic subgroup accuracy. This multimarker strategy may guide medical decision making, facilitate the use of MRI scanning, and prove valuable in the stratification of patients with brain injuries in future clinical trials.Classification of evidenceClass I evidence that blood concentrations of GFAP, tau, and NFL discriminate patients with mTBI with and without neuroimaging findings.

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