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dc.contributor.authorBlennow, Kaj
dc.contributor.authorDiaz-Lucena, Daniela
dc.contributor.authorZetterberg, Henrik
dc.contributor.authorVillar-Pique, Anna
dc.contributor.authorKarch, Andre
dc.contributor.authorVidal, Enric
dc.contributor.authorHermann, Peter
dc.contributor.authorSchmitz, Matthias
dc.contributor.authorFerrer Abizanda, Isidro
dc.contributor.authorZerr, Inga
dc.contributor.authorLlorens, Franc
dc.date.accessioned2020-09-22T15:16:34Z
dc.date.available2020-09-22T15:16:34Z
dc.date.issued2019-05-16
dc.identifier.citationJ Neurol Neurosurg Psychiatry. 2019 Aug;90(8):846-853. doi: 10.1136/jnnp-2018-320155. Epub 2019 May 16. PMID: 31097472..en_US
dc.identifier.pmid31097472
dc.identifier.doi10.1136/jnnp-2018-320155
dc.identifier.urihttp://hdl.handle.net/10033/622448
dc.description.abstractObjective: To investigate whether cerebrospinal fluid (CSF) neurogranin concentrations are altered in sporadic Creutzfeldt-Jakob disease (CJD), comparatively with Alzheimer's disease (AD), and associated with neuronal degeneration in brain tissue. Methods: CSF neurogranin, total tau, neurofilament light (NFL) and 14-3-3 protein were measured in neurological controls (NCs, n=64), AD (n=46) and CJD (n=81). The accuracy of neurogranin discriminating the three diagnostic groups was evaluated. Correlations between neurogranin and neurodegeneration biomarkers, demographic, genetic and clinical data were assessed. Additionally, neurogranin expression in postmortem brain tissue was studied. Results: Compared with NC, CSF neurogranin concentrations were increased in CJD (4.75 times of NC; p<0.001, area under curve (AUC), 0.96 (95% CI 0.93 to 0.99) and AD (1.94 times of NC; p<0.01, AUC 0.73, 95% CI 0.62 to 0.82), and were able to differentiate CJD from AD (p<0.001, AUC 0.85, 95% CI 0.78 to 0.92). CSF tau was increased in CJD (41 times of NC) and in AD (3.1 times of NC), both at p<0.001. In CJD, neurogranin positively correlated with tau (r=0.55, p<0.001) and was higher in 14-3-3-positivity (p<0.05), but showed no association with NFL (r=0.08, p=0.46). CJD-MM1/MV1 cases displayed higher neurogranin levels than VV2 cases. Neurogranin was increased at early CJD disease stages and was a good prognostic marker of survival time in CJD. In brain tissue, neurogranin was detected in the cytoplasm, membrane and postsynaptic density fractions of neurons, with reduced levels in AD, and more significantly in CJD, where they correlated with synaptic and axonal markers. Conclusions: Neurogranin is a new biomarker of prion pathogenesis with diagnostic and prognostic abilities, which reflects the degree of neuronal damage in brain tissue in a CJD subtype manner. Keywords: alzheimer’s disease; cerebrospinal fluid; creutzfeldt-jakob disease; neurodegenerative dementias; neurofilament light; neurogranin; tau.en_US
dc.language.isoenen_US
dc.publisherBMJ Publishing Groupen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectalzheimer’s diseaseen_US
dc.subjectcerebrospinal fluiden_US
dc.subjectcreutzfeldt-jakob diseaseen_US
dc.subjectneurodegenerative dementiasen_US
dc.subjectneurofilament lighten_US
dc.subjectneurograninen_US
dc.subjecttauen_US
dc.titleCSF neurogranin as a neuronal damage marker in CJD: a comparative study with AD.en_US
dc.typeArticleen_US
dc.identifier.eissn1468-330X
dc.contributor.departmentHZI, Helmholtz Zentrum für Infektionsforschung, GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.en_US
dc.identifier.journalJournal of neurology, neurosurgery, and psychiatryen_US
dc.source.volume90
dc.source.issue8
dc.source.beginpage846
dc.source.endpage853
refterms.dateFOA2020-09-22T15:16:35Z
dc.source.journaltitleJournal of neurology, neurosurgery, and psychiatry
dc.source.countryEngland


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