University of Nevada, Reno, School of Medicine, Reno, NV, USA.
Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
Exp Gerontol. 2022 Aug;165:111842. doi: 10.1016/j.exger.2022.111842. Epub 2022 May 24.
Lewy body dementia encompasses the common neurodegenerative disorders Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). Lewy Body disease (LBD) is characterized by abnormal aggregates of α-synuclein (α-syn) in the brain which form Lewy bodies. LBD is commonly misdiagnosed/underdiagnosed, especially in early stages. There remains a great need for reliable biomarkers to assist with LBD diagnosis. Amplification techniques such as real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA) represent an important advance for biomarker detection. Amplification assays detect the ability of pathogenic protein to induce conformational change in normal protein; α-syn has been shown to propagate in a prion-like manner, making it a candidate for such analysis. In this review, we describe the diagnostic potential of amplification techniques for differentiating α-synucleinopathies from other neurodegenerative disorders such as Alzheimer's disease (AD), frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and atypical parkinsonism, as well as α-synucleinopathies from each other. Recent studies report accurate detection of α-syn seeding activity in human tissues such as cerebrospinal fluid (CSF), submandibular gland (SMG), and posterior cervical skin. Adaptation to clinical settings may present challenges. However, the high accuracy of recent results, combined with the success of amplification assay diagnostics in clinical practice for Creutzfeldt-Jakob disease, suggest high promise for eventual clinical application.
路易体痴呆症包括常见的神经退行性疾病——路易体痴呆（DLB）和帕金森病痴呆（PDD）。路易体病（LBD）的特征是大脑中α-突触核蛋白（α-syn）的异常聚集，形成路易体。LBD 通常被误诊/漏诊，尤其是在早期阶段。因此，非常需要可靠的生物标志物来协助 LBD 诊断。扩增技术，如实时震颤诱导转化（RT-QuIC）和蛋白错误折叠循环扩增（PMCA），代表了生物标志物检测的重要进展。扩增检测法可检测致病蛋白诱导正常蛋白构象变化的能力；α-syn 以类朊病毒样方式传播，使其成为此类分析的候选者。在这篇综述中，我们描述了扩增技术在区分α-突触核蛋白病与其他神经退行性疾病（如阿尔茨海默病（AD）、额颞叶痴呆（FTD）、进行性核上性麻痹（PSP）、皮质基底节综合征（CBS）和非典型帕金森病）以及α-突触核蛋白病之间的诊断潜力。最近的研究报告称，在人组织（如脑脊液（CSF）、颌下腺（SMG）和颈后皮肤）中可以准确检测到α-syn 种籽活性。然而，适应临床环境可能会带来挑战。但是，最近的研究结果的高准确性，结合扩增检测法在克雅氏病临床实践中的成功，表明其在最终的临床应用方面具有很高的潜力。
