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dc.contributor.authorVillar-Piqué, Anna
dc.contributor.authorSchmitz, Matthias
dc.contributor.authorLachmann, Ingolf
dc.contributor.authorKarch, André
dc.contributor.authorCalero, Olga
dc.contributor.authorStehmann, Christiane
dc.contributor.authorSarros, Shannon
dc.contributor.authorLadogana, Anna
dc.contributor.authorPoleggi, Anna
dc.contributor.authorSantana, Isabel
dc.contributor.authorFerrer, Isidre
dc.contributor.authorMitrova, Eva
dc.contributor.authorŽáková, Dana
dc.contributor.authorPocchiari, Maurizio
dc.contributor.authorBaldeiras, Inês
dc.contributor.authorCalero, Miguel
dc.contributor.authorCollins, Steven J
dc.contributor.authorGeschwind, Michael D
dc.contributor.authorSánchez-Valle, Raquel
dc.contributor.authorZerr, Inga
dc.contributor.authorLlorens, Franc
dc.description.abstractCerebrospinal fluid (CSF) total prion protein (t-PrP) is decreased in sporadic Creutzfeldt-Jakob disease (sCJD). However, data on the comparative signatures of t-PrP across the spectrum of prion diseases, longitudinal changes during disease progression, and levels in pre-clinical cases are scarce. T-PrP was quantified in neurological diseases (ND, n = 147) and in prion diseases from different aetiologies including sporadic (sCJD, n = 193), iatrogenic (iCJD, n = 12) and genetic (n = 209) forms. T-PrP was also measured in serial lumbar punctures obtained from sCJD cases at different symptomatic disease stages, and in asymptomatic prion protein gene (PRNP) mutation carriers. Compared to ND, t-PrP concentrations were significantly decreased in sCJD, iCJD and in genetic prion diseases associated with the three most common mutations E200K, V210I (associated with genetic CJD) and D178N-129M (associated with fatal familial insomnia). In contrast, t-PrP concentrations in P102L mutants (associated with the Gerstmann-Sträussler-Scheinker syndrome) remained unaltered. In serial lumbar punctures obtained at different disease stages of sCJD patients, t-PrP concentrations inversely correlated with disease progression. Decreased mean t-PrP values were detected in asymptomatic D178-129M mutant carriers, but not in E200K and P102L carriers. The presence of low CSF t-PrP is common to all types of prion diseases regardless of their aetiology albeit with mutation-specific exceptions in a minority of genetic cases. In some genetic prion disease, decreased levels are already detected at pre-clinical stages and diminish in parallel with disease progression. Our data indicate that CSF t-PrP concentrations may have a role as a pre-clinical or early symptomatic diagnostic biomarker in prion diseases as well as in the evaluation of therapeutic interventions.en_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.subjectCerebrospinal fluiden_US
dc.subjectGenetic prion diseaseen_US
dc.subjectIatrogenic prion diseaseen_US
dc.subjectPrion proteinen_US
dc.subjectSporadic Creutzfeldt-Jakob diseaseen_US
dc.titleCerebrospinal Fluid Total Prion Protein in the Spectrum of Prion Diseases.en_US
dc.contributor.departmentHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.en_US
dc.source.journaltitleMolecular neurobiology

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