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Development of parallel reaction monitoring assays for cerebrospinal fluid proteins associated with Alzheimer's disease

Artikel i vetenskaplig tidskrift
Författare A. Andersson
J. Remnestål
Bengt Nellgård
H. Vunk
D. Kotol
F. Edfors
M. Uhlén
J. M. Schwenk
L. L. Ilag
Henrik Zetterberg
Kaj Blennow
A. Månberg
P. Nilsson
C. Fredolini
Publicerad i Clinica Chimica Acta
Volym 494
Nummer/häfte July
Sidor 79-93
ISSN 0009-8981
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi
Institutionen för kliniska vetenskaper, Avdelningen för anestesiologi och intensivvård
Sidor 79-93
Språk en
Länkar dx.doi.org/10.1016/j.cca.2019.03.24...
Ämnesord 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
Ämneskategorier Neurovetenskaper

Sammanfattning

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. © 2019 The Authors

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