致死性家族性失眠
无症状携带者
脑脊液
PRNP公司
无症状的
疾病
病理
医学
突变
神经学
突变体
朊蛋白
免疫学
病毒学
生物
基因
遗传学
精神科
作者
Anna Villar‐Piqué,Matthias Schmitz,Ingolf Lachmann,André Karch,Olga Calero,Christiane Stehmann,Shannon Sarros,Anna Ladogana,Anna Poleggi,Isabel Santana,Isidre Ferrer,E Mitrová,Dana Žáková,Maurizio Pocchiari,Inês Baldeiras,Miguel Calero,Steven Collins,Michael D. Geschwind,Raquel Sánchez‐Valle,Inga Zerr,Franc Llorens
标识
DOI:10.1007/s12035-018-1251-1
摘要
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.
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