Serum biomarkers of neuroinflammation and blood-brain barrier leakage in amyotrophic lateral sclerosis

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dc.citation.issue1
dc.citation.volume22
dc.contributor.authorCao MC
dc.contributor.authorCawston EE
dc.contributor.authorChen G
dc.contributor.authorBrooks C
dc.contributor.authorDouwes J
dc.contributor.authorMcLean D
dc.contributor.authorGraham ES
dc.contributor.authorDragunow M
dc.contributor.authorScotter EL
dc.coverage.spatialEngland
dc.date.accessioned2023-06-21T21:31:59Z
dc.date.available2022-06-11
dc.date.available2022-03-07
dc.date.available2023-06-21T21:31:59Z
dc.date.issued2022-12
dc.description(c) The Author/s 2022
dc.description.abstractAmyotrophic lateral sclerosis (ALS) is an incurable and rapidly progressive neurological disorder. Biomarkers are critical to understanding disease causation, monitoring disease progression and assessing the efficacy of treatments. However, robust peripheral biomarkers are yet to be identified. Neuroinflammation and breakdown of the blood-brain barrier (BBB) are common to familial and sporadic ALS and may produce a unique biomarker signature in peripheral blood. Using cytometric bead array (n = 15 participants per group (ALS or control)) and proteome profiling (n = 6 participants per group (ALS or control)), we assessed a total of 106 serum cytokines, growth factors, and BBB breakdown markers in the serum of control and ALS participants. Further, primary human brain pericytes, which maintain the BBB, were used as a biosensor of inflammation following pre-treatment with ALS serum. Principal components analysis of all proteome profile data showed no clustering of control or ALS sera, and no individual serum proteins met the threshold for statistical difference between ALS and controls (adjusted P values). However, the 20 most changed proteins between control and ALS sera showed a medium effect size (Cohen's d = 0.67) and cluster analysis of their levels together identified three sample subsets; control-only, mixed control-ALS, and ALS-only. These 20 proteins were predominantly pro-angiogenic and growth factors, including fractalkine, BDNF, EGF, PDGF, Dkk-1, MIF and angiopoietin-2. S100β, a protein highly concentrated in glial cells and therefore a marker of BBB leakage when found in blood, was unchanged in ALS serum, suggesting that serum protein profiles were reflective of peripheral rather than CNS biofluids. Finally, primary human brain pericytes remained proliferative and their secretome was unchanged by chronic exposure to ALS serum. Our exploratory study suggests that individual serum cytokine levels may not be robust biomarkers in small studies of ALS, but that larger studies using multiplexed analysis of pro-angiogenic and growth factors may identify a peripheral signature of ALS pathogenesis.
dc.description.publication-statusPublished online
dc.format.extent216 - ?
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/35690735
dc.identifier10.1186/s12883-022-02730-1
dc.identifier.citationBMC Neurol, 2022, 22 (1), pp. 216 - ?
dc.identifier.doi10.1186/s12883-022-02730-1
dc.identifier.eissn1471-2377
dc.identifier.elements-id453898
dc.identifier.harvestedMassey_Dark
dc.identifier.urihttps://hdl.handle.net/10179/18329
dc.languageeng
dc.publisherBioMed Central Ltd
dc.relation.isPartOfBMC Neurol
dc.subjectAmyotrophic lateral sclerosis
dc.subjectBlood-brain barrier
dc.subjectCytokine
dc.subjectNeuroinflammation
dc.subjectSerum
dc.subjectAmyotrophic Lateral Sclerosis
dc.subjectBiomarkers
dc.subjectBlood-Brain Barrier
dc.subjectCytokines
dc.subjectHumans
dc.subjectIntercellular Signaling Peptides and Proteins
dc.subjectNeuroinflammatory Diseases
dc.subjectProteome
dc.subject.anzsrc1109 Neurosciences
dc.subject.anzsrc1702 Cognitive Sciences
dc.titleSerum biomarkers of neuroinflammation and blood-brain barrier leakage in amyotrophic lateral sclerosis
dc.typeJournal article
pubs.notesNot known
pubs.organisational-group/Massey University
pubs.organisational-group/Massey University/College of Health
pubs.organisational-group/Massey University/College of Health/Research Centre for Hauora and Health
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