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  • Paterson, R. W.,University College London (författare)

A targeted proteomic multiplex CSF assay identifies increased malate dehydrogenase and other neurodegenerative biomarkers in individuals with Alzheimer's disease pathology.

  • E-artikel/E-kapitelEngelska2016

Nummerbeteckningar

  • LIBRIS-ID:oai:gup.ub.gu.se/253388
  • 84996837299scopus
  • 85033561456scopus
  • 27845782pmid
  • 27845782pmid
  • 10.1038/tp.2016.194doi

Ingår i deldatabas

Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • Published
  • 15
  • not verified at registration
  • Alzheimer's disease (AD) is the most common cause of dementia. Biomarkers are required to identify individuals in the preclinical phase, explain phenotypic diversity, measure progression and estimate prognosis. The development of assays to validate candidate biomarkers is costly and time-consuming. Targeted proteomics is an attractive means of quantifying novel proteins in cerebrospinal and other fluids, and has potential to help overcome this bottleneck in biomarker development. We used a previously validated multiplexed 10-min, targeted proteomic assay to assess 54 candidate cerebrospinal fluid (CSF) biomarkers in two independent cohorts comprising individuals with neurodegenerative dementias and healthy controls. Individuals were classified as 'AD' or 'non-AD' on the basis of their CSF T-tau and amyloid Aβ1-42 profile measured using enzyme-linked immunosorbent assay; biomarkers of interest were compared using univariate and multivariate analyses. In all, 35/31 individuals in Cohort 1 and 46/36 in Cohort 2 fulfilled criteria for AD/non-AD profile CSF, respectively. After adjustment for multiple comparisons, five proteins were elevated significantly in AD CSF compared with non-AD CSF in both cohorts: malate dehydrogenase; total APOE; chitinase-3-like protein 1 (YKL-40); osteopontin and cystatin C. In an independent multivariate orthogonal projection to latent structures discriminant analysis (OPLS-DA), these proteins were also identified as major contributors to the separation between AD and non-AD in both cohorts. Independent of CSF Aβ1-42 and tau, a combination of these biomarkers differentiated AD and non-AD with an area under curve (AUC)=0.88. This targeted proteomic multiple reaction monitoring (MRM)-based assay can simultaneously and rapidly measure multiple candidate CSF biomarkers. Applying this technique to AD we demonstrate differences in proteins involved in glucose metabolism and neuroinflammation that collectively have potential clinical diagnostic utility.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Heywood, W. E.,University College London(SwePub:) (författare)
  • Heslegrave, A. J.,University College London(SwePub:) (författare)
  • Magdalinou, N. K.,University College London(SwePub:) (författare)
  • Andreasson, U.,Sahlgrenska University Hospital(SwePub:) (författare)
  • Sirka, E.,University College London(SwePub:) (författare)
  • Bliss, E.,University College London(SwePub:) (författare)
  • Slattery, C. F.,University College London(SwePub:) (författare)
  • Toombs, J.,University College London(SwePub:) (författare)
  • Svensson, J.,Sahlgrenska Academy, Skaraborg Hospital(SwePub:) (författare)
  • Johansson, P.,Skaraborg Hospital, Sahlgrenska Academy(SwePub:) (författare)
  • Fox, N. C.,University College London(SwePub:) (författare)
  • Zetterberg, H.,University College London, Sahlgrenska University Hospital(SwePub:) (författare)
  • Mills, K.,University College London(SwePub:) (författare)
  • Schott, J. M.,University College London(SwePub:) (författare)
  • Göteborgs universitet.Sahlgrenska akademin.Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi.(SwePub:gu.se)1630
  • Gothenburg University.Sahlgrenska Academy.Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry.(SwePub:gu.se)1630
  • Göteborgs universitet.Sahlgrenska akademin.Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition.(SwePub:gu.se)1793
  • Gothenburg University.Sahlgrenska Academy.Institute of Medicine, Department of Internal Medicine and Clinical Nutrition.(SwePub:gu.se)1793

Sammanhörande titlar

  • Ingår i:Translational psychiatry2158-31886:11

Internetlänk

  • http://dx.doi.org/10.1038/tp.2016.194fulltext
  • https://lup.lub.lu.se/record/b88d23ef-e620-428e-ae1a-deea01282aa6Till lärosätets (lu) databas
  • https://gup.ub.gu.se/publication/253388Till lärosätets (gu) databas

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