Comparison between plasma and cerebrospinal fluid biomarkers for the early diagnosis and association with survival in prion disease
Comparison between plasma and cerebrospinal fluid biomarkers for the early diagnosis and association with survival in prion disease
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DOI：
10.1136/jnnp-2020-323826
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发表时间：
2020-11-01
影响因子：
11
通讯作者：
Parchi, Piero
中科院分区：
文献类型：
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作者：
Abu-Rumeileh, Samir;Baiardi, Simone;Parchi, Piero
目的比较血液和脑脊液（CSF）检测对不同亚型朊病毒病的诊断准确性和预后价值。方法采用单分子免疫测定法检测336例朊病毒病患者血浆tau蛋白和神经丝轻链（NfL）蛋白水平，并检测CSF总（t）-tau蛋白、NfL蛋白和蛋白14-3-3水平。非朊病毒快速进展性痴呆（n=106）和非神经变性对照（n=37）。然后，我们评估了每个血浆和CSF标记物的诊断和生存的关联，考虑到疾病亚型，这是一个强大的独立预后因素在朊病毒diseases.Results血浆tau蛋白和NfL浓度较高的朊病毒疾病患者比非神经退行性疾病的控制和非朊病毒快速进展性痴呆。血浆tau显示出比血浆NfL更高的诊断价值，但比CSF蛋白t-tau和14-3-3更低的准确性。在整个朊病毒队列中，血浆（tau和NfL）和CSF（t-tau，14-3-3和NfL）标志物均与生存率显著相关，并显示出相似的预后值。亚型内分析显示，仅散发性克雅氏病（sCJD）MM（V）1的CSF t-tau蛋白、sCJD VV 2的血浆tau蛋白和CSF t-tau蛋白以及缓慢进展性朊病毒病的血浆NfL蛋白与生存率显著相关。血浆tau和NfL以及CSF t-tau以亚型特异性方式与朊病毒疾病中的存活率显著相关，并且可用于改善临床试验分层和临床护理。
Objective To compare the diagnostic accuracy and the prognostic value of blood and cerebrospinal fluid (CSF) tests across prion disease subtypes.Methods We used a single-molecule immunoassay to measure tau and neurofilament light chain (NfL) protein levels in the plasma and assessed CSF total(t)-tau, NfL and protein 14-3-3 levels in patients with prion disease (n=336), non-prion rapidly progressive dementias (n=106) and non-neurodegenerative controls (n=37). We then evaluated each plasma and CSF marker for diagnosis and their association with survival, taking into account the disease subtype, which is a strong independent prognostic factor in prion disease.Results Plasma tau and NfL concentrations were higher in patients with prion disease than in non-neurodegenerative controls and non-prion rapidly progressive dementias. Plasma tau showed higher diagnostic value than plasma NfL, but a lower accuracy than the CSF proteins t-tau and 14-3-3. In the whole prion cohort, both plasma (tau and NfL) and CSF (t-tau, 14-3-3 and NfL) markers were significantly associated with survival and showed similar prognostic values. However, the intrasubtype analysis revealed that only CSF t-tau in sporadic Creutzfeldt-Jakob disease (sCJD) MM(V)1, plasma tau and CSF t-tau in sCJD VV2, and plasma NfL in slowly progressive prion diseases were significantly associated with survival after accounting for covariates.Conclusions Plasma markers have lower diagnostic accuracy than CSF biomarkers. Plasma tau and NfL and CSF t-tau are significantly associated with survival in prion disease in a subtype-specific manner and can be used to improve clinical trial stratification and clinical care.