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Development of parallel reaction monitoring assays for cerebrospinal fluid proteins associated with Alzheimer's disease
KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinity Proteomics. KTH, Centra, Science for Life Laboratory, SciLifeLab.
KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
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2019 (engelsk)Inngår i: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 494, s. 79-93Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Detailed knowledge of protein changes in cerebrospinal fluid (CSF) across healthy and diseased individuals would provide a better understanding of the onset and progression of neurodegenerative disorders. In this study, we selected 20 brain-enriched proteins previously identified in CSF by antibody suspension bead arrays (SBA) to be potentially biomarkers for Alzheimer's disease (AD) and verified these using an orthogonal approach. We examined the same set of 94 CSF samples from patients affected by AD (including preclinical and prodromal), mild cognitive impairment (MCI), non-AD dementia and healthy individuals, which had previously been analyzed by SBA. Twenty-eight parallel reaction monitoring (PRM) assays were developed and 13 of them could be validated for protein quantification. Antibody profiles were verified by PRM. For seven proteins, the antibody profiles were highly correlated with the PRM results (r > 0.7) and GAP43, VCAM1 and PSAP were identified as potential markers of preclinical AD. In conclusion, we demonstrate the usefulness of targeted mass spectrometry as a tool for the orthogonal verification of antibody profiling data, suggesting that these complementary methods can be successfully applied for comprehensive exploration of CSF protein levels in neurodegenerative disorders.

sted, utgiver, år, opplag, sider
Elsevier B.V. , 2019. Vol. 494, s. 79-93
Emneord [en]
AD, Alzheimer's disease, Biomarkers, Cerebrospinal fluid, Parallel reaction monitoring (PRM), Suspension bead array (SBA), alpha 1 aantitrypsin, alpha 1 antichymotrypsin, apolipoprotein, biological marker, cathepsin D, cholecystokinin, creatine kinase B type, dickkopf related protein 3, fibrinogen alpha, fructose bisphosphate aldolase C, glucose regulated protein 94, inter alpha trypsin inhibitor heavy chain H1, leucine rich alpha 2 glycoprotein, neurobeachin, neurofilament medium polypeptide, neuromodulin, plasminogen, prosaposin, protein S100B, SPARC like protein 1, unclassified drug, vascular cell adhesion protein 1, adult, aged, Alzheimer disease, Article, clinical article, cohort analysis, controlled study, correlational study, disease course, female, human, male, mass spectrometry, middle aged, mild cognitive impairment, multiple reaction monitoring, priority journal, protein blood level, protein cerebrospinal fluid level, protein microarray, suspension bead array, very elderly
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Identifikatorer
URN: urn:nbn:se:kth:diva-252444DOI: 10.1016/j.cca.2019.03.243ISI: 000470950400013Scopus ID: 2-s2.0-85063002689OAI: oai:DiVA.org:kth-252444DiVA, id: diva2:1337494
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QC 20190715

Tilgjengelig fra: 2019-07-15 Laget: 2019-07-15 Sist oppdatert: 2020-01-10bibliografisk kontrollert

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Remnestål, JuliaVunk, HelianEdfors, FredrikUhlén, MathiasSchwenk, Jochen M.Månberg, AnnaNilsson, PeterFredolini, Claudia

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Andersson, AnnikaRemnestål, JuliaVunk, HelianKotol, DavidEdfors, FredrikUhlén, MathiasSchwenk, Jochen M.Månberg, AnnaNilsson, PeterFredolini, Claudia
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