National Reference Center for Transmissible Spongiform Encephalopathies, Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH, USA; Departments of Neurology, Psychiatry, and Pathology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA.
Lancet Neurol. 2021 Mar;20(3):235-246. doi: 10.1016/S1474-4422(20)30477-4.
Sporadic Creutzfeldt-Jakob disease is a fatal neurodegenerative disease caused by misfolded prion proteins (PrP). Effective therapeutics are currently not available and accurate diagnosis can be challenging. Clinical diagnostic criteria use a combination of characteristic neuropsychiatric symptoms, CSF proteins 14-3-3, MRI, and EEG. Supportive biomarkers, such as high CSF total tau, could aid the diagnostic process. However, discordant studies have led to controversies about the clinical value of some established surrogate biomarkers. Development and clinical application of disease-specific protein aggregation and amplification assays, such as real-time quaking induced conversion (RT-QuIC), have constituted major breakthroughs for the confident pre-mortem diagnosis of sporadic Creutzfeldt-Jakob disease. Updated criteria for the diagnosis of sporadic Creutzfeldt-Jakob disease, including application of RT-QuIC, should improve early clinical confirmation, surveillance, assessment of PrP seeding activity in different tissues, and trial monitoring. Moreover, emerging blood-based, prognostic, and potentially pre-symptomatic biomarker candidates are under investigation.
散发性克雅氏病是一种由错误折叠的朊病毒蛋白（PrP）引起的致命神经退行性疾病。目前尚无有效的治疗方法，且诊断存在一定难度。临床诊断标准结合了特征性神经精神症状、脑脊液蛋白 14-3-3、MRI 和 EEG。支持性生物标志物，如高脑脊液总tau，可辅助诊断过程。然而，存在不一致的研究结果，导致一些既定替代生物标志物的临床价值存在争议。疾病特异性蛋白聚集和扩增检测方法的开发和临床应用，如实时震颤诱导转换（RT-QuIC），为散发性克雅氏病的可靠生前诊断带来了重大突破。更新的散发性克雅氏病诊断标准，包括 RT-QuIC 的应用，有望改善早期临床确诊、监测、不同组织中 PrP 播种活性的评估以及临床试验监测。此外，正在研究新兴的基于血液的、预后和潜在的症状前生物标志物候选物。
