Rissardo Jamir Pitton, Caprara Ana Leticia Fornari
Neurology Department, Cooper University Hospital, Camden, NJ 08103, USA.
Clin Pract. 2025 Mar 17;15(3):65. doi: 10.3390/clinpract15030065.
Alpha-synuclein has been associated with neurodegeneration, especially in Parkinson's disease (PD). This study aimed to review clinical, biochemical, and neuroimaging markers and management of prodromal synucleinopathies. The prodromal state of synucleinopathies can be better understood with PD pathophysiology, and it can be separated into premotor and pre-diagnostic phases. The incidence of PD in patients with prodromal phase symptoms ranges from 0.07 to 14.30, and the most frequently studied pathology is the REM behavioral disorder (RBD). Neuroimaging markers are related to dopamine denervation, brain perfusion changes, gross anatomy changes, and peripheral abnormalities. α-synuclein assays (SAA) in CSF revealed high sensitivity (up to 97%) and high specificity (up to 92%); in the last decade, there was the development of other matrices (blood, skin, and olfactory mucosa) for obtaining quantitative and qualitative α-synuclein. Other biomarkers are neurofilament light chain, DOPA decarboxylase, and multiplexed mass spectrometry assay. Regarding genetic counseling in α-synucleinopathies, it is an important topic in clinical practice to discuss with patients with high-risk individuals and should involve basic principles of autonomy, beneficence, and non-maleficence. Some of the themes that should be reviewed are the involvement of physical activity, diet (including alcohol, coffee, and vitamin supplementation), smoking, sleep, and stress in the pathophysiology of synucleinopathies. The number of trials related to prodromal symptoms is still scarce, and the number of studies evaluating intervention is even lower.
α-突触核蛋白与神经退行性变有关，尤其是在帕金森病（PD）中。本研究旨在综述前驱性突触核蛋白病的临床、生化和神经影像学标志物及管理。通过PD的病理生理学可以更好地理解突触核蛋白病的前驱状态，它可分为运动前期和诊断前期阶段。出现前驱期症状的患者中PD的发病率为0.07至14.30，研究最多的病理表现是快速眼动睡眠行为障碍（RBD）。神经影像学标志物与多巴胺去神经支配、脑灌注变化、大体解剖结构变化及外周异常有关。脑脊液中的α-突触核蛋白检测（SAA）显示出高敏感性（高达97%）和高特异性（高达92%）；在过去十年中，还开发了其他基质（血液、皮肤和嗅黏膜）来获取定量和定性的α-突触核蛋白。其他生物标志物有神经丝轻链、多巴脱羧酶和多重质谱分析。关于突触核蛋白病的遗传咨询，与高危个体患者进行讨论是临床实践中的一个重要话题，应涉及自主、行善和不伤害的基本原则。一些应探讨的主题包括身体活动、饮食（包括酒精、咖啡和维生素补充）、吸烟、睡眠和压力在突触核蛋白病病理生理学中的作用。与前驱症状相关的试验数量仍然很少，评估干预措施的研究数量甚至更少。
