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Title:	Cerebrospinal fluid total prion protein in the spectrum of prion diseases
Author:	Villar Piqué, Anna; Schmitz, Matthias; Lachmann, Ingolf; Karch, André; Calero, Olga; Stehmann, Christ; Sarros, Shannon; Ladogana, Anna Sánchez; Poleggi, Anna; Santana, Isabel; Ferrer, Isidro (Ferrer Abizanda); Mitrova, Eva; Žáková, Dana; Pocchiari, Maurizio; Baldeiras, Inês; Calero, Miguel; Collins, Steven J.; Geschwind, Michael D.; Sánchez del Valle Díaz, Raquel; Zerr, Inga; Llorens Torres, Franc
Notes:	Cerebrospinal 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.
Subject(s):	-Malalties per prions -Líquid cefalorraquidi -Patologia -Prion diseases -Cerebrospinal fluid -Pathology
Rights:	(c) Humana Press., 2019
Document type:	Article Article - Accepted version
Published by:	Humana Press.
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