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FältnamnIndikatorerMetadata
00005659naa a2200553 4500
001oai:gup.ub.gu.se/253388
003SwePub
008240528s2016 | |||||||||||000 ||eng|
024a https://gup.ub.gu.se/publication/2533882 URI
024a https://doi.org/10.1038/tp.2016.1942 DOI
040 a (SwePub)gu
041 a eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
100a Paterson, R W4 aut
2451 0a A targeted proteomic multiplex CSF assay identifies increased malate dehydrogenase and other neurodegenerative biomarkers in individuals with Alzheimer's disease pathology.
264 c 2016-11-15
264 1b Springer Science and Business Media LLC,c 2016
520 a 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.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Neurologi0 (SwePub)302072 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Neurology0 (SwePub)302072 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Endokrinologi och diabetes0 (SwePub)302052 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Endocrinology and Diabetes0 (SwePub)302052 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Annan klinisk medicin0 (SwePub)302992 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Other Clinical Medicine0 (SwePub)302992 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Klinisk laboratoriemedicin0 (SwePub)302232 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Clinical Laboratory Medicine0 (SwePub)302232 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Psykiatri0 (SwePub)302152 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Psychiatry0 (SwePub)302152 hsv//eng
700a Heywood, W E4 aut
700a Heslegrave, A J4 aut
700a Magdalinou, N K4 aut
700a Andreasson, Ulf,d 1968u Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry4 aut0 (Swepub:gu)xaulfz
700a Sirka, E4 aut
700a Bliss, E4 aut
700a Slattery, C F4 aut
700a Toombs, J4 aut
700a Svensson, Johan,d 1964u Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition4 aut0 (Swepub:gu)xsjohc
700a Johansson, Per,d 1966u Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition4 aut0 (Swepub:gu)xjperq
700a Fox, N C4 aut
700a Zetterberg, Henrik,d 1973u Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry4 aut0 (Swepub:gu)xzethe
700a Mills, K4 aut
700a Schott, J M4 aut
710a Göteborgs universitetb Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi4 org
773t Translational psychiatryd : Springer Science and Business Media LLCg 6:11q 6:11x 2158-3188
856u https://doi.org/10.1038/tp.2016.194
8564 8u https://gup.ub.gu.se/publication/253388
8564 8u https://doi.org/10.1038/tp.2016.194

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