Dataset Information

Plasma NfL and GFAP as biomarkers of spinal cord degeneration in adrenoleukodystrophy.

ABSTRACT: OBJECTIVE:To explore the potential of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) as biomarkers of spinal cord degeneration in adrenoleukodystrophy, as objective treatment-outcome parameters are needed. METHODS:Plasma NfL and GFAP levels were measured in 45 male and 47 female ALD patients and compared to a reference cohort of 73 healthy controls. For male patients, cerebrospinal fluid (CSF) samples (n = 33) and 1-year (n = 39) and 2-year (n = 18) follow-up data were also collected. Severity of myelopathy was assessed with clinical parameters: Expanded Disability Status Scale (EDSS), Severity Scoring system for Progressive Myelopathy (SSPROM), and timed up-and-go. RESULTS:NfL and GFAP levels were higher in male (P < 0.001, effect size (partial ?2 ) NfL = 0.49, GFAP = 0.13) and female (P < 0.001, effect size NfL = 0.19, GFAP = 0.23) patients compared to controls; levels were higher in both symptomatic and asymptomatic patients. In male patients, NfL levels were associated with all three clinical parameters of severity of myelopathy (EDSS, SSPROM, and timed up-and go), while GFAP in male and NfL and GFAP in female patients were not. Changes in clinical parameters during follow-up did not correlate with (changes in) NfL or GFAP levels. Plasma and CSF NfL were strongly correlated (r = 0.60, P < 0.001), but plasma and CSF GFAP were not (r = 0.005, P = 0.98). INTERPRETATION:Our study illustrates the potential of plasma NfL as biomarker of spinal cord degeneration in adrenoleukodystrophy, which was superior to plasma GFAP in our cohort.

SUBMITTER: van Ballegoij WJC

PROVIDER: S-EPMC7664277 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Plasma NfL and GFAP as biomarkers of spinal cord degeneration in adrenoleukodystrophy.

van Ballegoij Wouter J C WJC van de Stadt Stephanie I W SIW Huffnagel Irene C IC Kemp Stephan S Willemse Eline A J EAJ Teunissen Charlotte E CE Engelen Marc M

Annals of clinical and translational neurology 20201013 11

<h4>Objective</h4>To explore the potential of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) as biomarkers of spinal cord degeneration in adrenoleukodystrophy, as objective treatment-outcome parameters are needed.<h4>Methods</h4>Plasma NfL and GFAP levels were measured in 45 male and 47 female ALD patients and compared to a reference cohort of 73 healthy controls. For male patients, cerebrospinal fluid (CSF) samples (n = 33) and 1-year (n = 39) and 2-year (n = 18) follow-up ...[more]

PMID: 33047897

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Project description:Objective biomarkers for Parkinson's Disease (PD) could aid early and specific diagnosis, effective monitoring of disease progression, and improved design and interpretation of clinical trials. Although alpha-synuclein remains a biomarker candidate of interest, the multifactorial and heterogenous nature of PD highlights the need for a PD biomarker panel. Ideal biomarker candidates include markers that are detectable in easily accessible samples, (ideally blood) and that reflect the underlying pathological process of PD. In the present study, we explored the diagnostic and prognostic PD biomarker potential of the SIMOA neurology 4-plex-A biomarker panel, which included neurofilament light (NFL), glial fibrillary acid protein (GFAP), tau and ubiquitin C-terminal hydrolase L1 (UCHL-1). We initially performed a serum vs plasma comparative study to determine the most suitable blood-based matrix for the measurement of these proteins in a multiplexed assay. The levels of NFL and GFAP in plasma and serum were highly correlated (Spearman rho-0.923, p < 0.0001 and rho = 0.825, p < 0.001 respectively). In contrast, the levels of tau were significantly higher in plasma compared to serum samples (p < 0.0001) with no correlation between sample type (Spearman p > 0.05). The neurology 4-plex-A panel, along with plasma alpha-synuclein was then assessed in a cross-sectional cohort of 29 PD patients and 30 controls. Plasma NFL levels positively correlated with both GFAP and alpha-synuclein levels (rho = 0.721, p < 0.0001 and rho = 0.390, p < 0.05 respectively). As diagnostic biomarkers, the control and PD groups did not differ in their mean NFL, GFAP, tau or UCHL-1 plasma levels (t test p > 0.05). As disease state biomarkers, motor severity (MDS-UPDRS III) correlated with increased NFL (rho = 0.646, p < 0.0001), GFAP (rho = 0.450, p < 0.05) and alpha-synuclein levels (rho = 0.406, p < 0.05), while motor stage (Hoehn and Yahr) correlated with increased NFL (rho = 0.455, p < 0.05) and GFAP (rho = 0.549, p < 0.01) but not alpha-synuclein levels (p > 0.05). In conclusion, plasma was determined to be most suitable blood-based matrix for multiplexing the neurology 4-plex-A panel. Given their correlation with motor features of PD, NFL and GFAP appear to be promising disease state biomarker candidates and further longitudinal validation of these two proteins as blood-based biomarkers for PD progression is warranted.

Project description:BackgroundNeuroinflammation and neuronal injury have been reported to be associated with the development of postoperative delirium in both preclinical and clinical settings. This study aimed to investigate the potential correlation between biomarkers of neurofilament light chain and glial fibrillary acidic protein and emergence and postoperative delirium in elderly patients undergoing surgery.MethodsPatients who developed emergence delirium (n = 30) and postoperative delirium (n = 32), along with their matched controls, were enrolled after obtaining ethics approval and written informed consent. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit or Confusion Assessment Method scale, and blood samples were collected before and after surgery for plasma neurofilament light chain and glial fibrillary acidic protein measurements using a single-molecule array.ResultsThe study found that in patients with emergence delirium, the increase in plasma neurofilament light chain protein levels during surgery was significantly higher than in non-delirium patients (P = 0.002). Additionally, in patients with postoperative delirium, both the increase in plasma neurofilament light chain protein levels (P < 0.001) and the increase in plasma glial fibrillary acidic protein levels during surgery (P = 0.008) were significantly higher than in non-delirium patients. Multivariate logistic regression analysis showed that the increase in plasma neurofilament light chain protein was associated with emergence delirium (adjusted OR = 1.872, P = 0.005), and the increase in plasma glial fibrillary acidic protein was associated with postoperative delirium (adjusted OR = 1.419, P = 0.016). Moreover, the American Society of Anesthesiologists Physical Status Classification and surgical duration were also found to be associated with delirium in elderly patients.ConclusionOur findings suggest that emergence delirium is linked to elevated levels of neurofilament light chain, a biomarker of axonal injury, during surgery. Furthermore, in addition to axonal injury, postoperative delirium was also associated with an increase in glial fibrillary acidic protein, a marker of astrocyte activation.

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Dataset Information

Plasma NfL and GFAP as biomarkers of spinal cord degeneration in adrenoleukodystrophy.

Publications

Plasma NfL and GFAP as biomarkers of spinal cord degeneration in adrenoleukodystrophy.

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