期刊
MOLECULAR NEUROBIOLOGY
卷 56, 期 4, 页码 2811-2821出版社
SPRINGER
DOI: 10.1007/s12035-018-1251-1
关键词
Cerebrospinal fluid; Prion protein; Sporadic Creutzfeldt-Jakob disease; Genetic prion disease; Iatrogenic prion disease
资金
- Robert Koch Institute through funds from the Federal Ministry of Health of Germany [1369-341]
- Spanish Ministry of Health - Instituto Carlos III/Fondo Social Europeo [CP16/00041]
- Fondo Europeo de Desarrollo Regional (FEDER) through the Interreg V-A Espana-Francia-Andorra (POCTEFA 2014-2020) programme
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-Straussler-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据