TY - JOUR
T1 - Cerebrospinal Fluid Total Prion Protein in the Spectrum of Prion Diseases
AU - Villar-Piqué, Anna
AU - Schmitz, Matthias
AU - Lachmann, Ingolf
AU - Karch, André
AU - Calero, Olga
AU - Stehmann, Christiane
AU - Sarros, Shannon
AU - Ladogana, Anna
AU - Poleggi, Anna
AU - Santana, Isabel
AU - Ferrer, Isidre
AU - Mitrova, Eva
AU - Žáková, Dana
AU - Pocchiari, Maurizio
AU - Baldeiras, Inês
AU - Calero, Miguel
AU - Collins, Steven J
AU - Geschwind, Michael D
AU - Sánchez-Valle, Raquel
AU - Zerr, Inga
AU - Llorens, Franc
PY - 2019/4
Y1 - 2019/4
N2 - 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.
AB - 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.
KW - Aged
KW - Codon/genetics
KW - Disease Progression
KW - Female
KW - Heterozygote
KW - Humans
KW - Male
KW - Middle Aged
KW - Mutation/genetics
KW - Prion Diseases/cerebrospinal fluid
KW - Prion Proteins/cerebrospinal fluid
U2 - 10.1007/s12035-018-1251-1
DO - 10.1007/s12035-018-1251-1
M3 - Article
C2 - 30062673
VL - 56
SP - 2811
EP - 2821
JO - Molecular Neurobiology
JF - Molecular Neurobiology
SN - 0893-7648
IS - 4
ER -