Poleggi Anna, Baiardi Simone, Ladogana Anna, Parchi Piero
Unit of Clinic, Diagnostics and Therapy of the Central Nervous System Diseases, Department of Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
Front Aging Neurosci. 2022 Apr 25;14:874734. doi: 10.3389/fnagi.2022.874734. eCollection 2022.
Prion diseases are rapidly progressive, invariably fatal, transmissible neurodegenerative disorders associated with the accumulation of the amyloidogenic form of the prion protein in the central nervous system (CNS). In humans, prion diseases are highly heterogeneous both clinically and neuropathologically. Prion diseases are challenging to diagnose as many other neurologic disorders share the same symptoms, especially at clinical onset. Definitive diagnosis requires brain autopsy to identify the accumulation of the pathological prion protein, which is the only specific disease biomarker. Although brain post-mortem investigation remains the gold standard for diagnosis, antemortem clinical, instrumental, and laboratory tests showing variable sensitivities and specificity, being surrogate disease biomarkers, have been progressively introduced in clinical practice to reach a diagnosis. More recently, the ultrasensitive Real-Time Quaking-Induced Conversion (RT-QuIC) assay, exploiting, for the first time, the detection of misfolded prion protein through an amplification strategy, has highly improved the "in-vitam" diagnostic process, reaching in cerebrospinal fluid (CSF) and olfactory mucosa (OM) around 96% sensitivity and close to 100% specificity. RT-QuIC also improved the detection of the pathologic prion protein in several peripheral tissues, possibly even before the clinical onset of the disease. The latter aspect is of great interest for the early and even preclinical diagnosis in subjects at genetic risk of developing the disease, who will likely be the main target population in future clinical trials. This review presents an overview of the current knowledge and future perspectives on using RT-QuIC to diagnose human prion diseases.
朊病毒病是一种快速进展、 invariably fatal、可传播的神经退行性疾病，与朊病毒蛋白的淀粉样变形式在中枢神经系统（CNS）中的积累有关。在人类中，朊病毒病在临床和神经病理学上具有高度异质性。由于许多其他神经系统疾病具有相同的症状，尤其是在临床发病时，因此朊病毒病的诊断具有挑战性。明确诊断需要进行脑尸检以确定病理性朊病毒蛋白的积累，这是唯一的特异性疾病生物标志物。尽管脑死后调查仍然是诊断的金标准，但作为替代疾病生物标志物的生前临床、仪器和实验室检查显示出不同的敏感性和特异性，已逐渐引入临床实践以进行诊断。最近，超灵敏的实时震颤诱导转化（RT-QuIC）检测方法首次利用扩增策略检测错误折叠的朊病毒蛋白，极大地改进了“活体”诊断过程，在脑脊液（CSF）和嗅黏膜（OM）中的敏感性达到约96%，特异性接近100%。RT-QuIC还提高了在几种外周组织中病理性朊病毒蛋白的检测率，甚至可能在疾病临床发作之前。后一个方面对于有患该病遗传风险的受试者的早期甚至临床前诊断非常重要，这些受试者可能是未来临床试验的主要目标人群。本综述概述了使用RT-QuIC诊断人类朊病毒病的当前知识和未来前景。
