Bruschi Giulia, Bortolin Elisa, Mazzeo Salvatore, Bombaci Alessandro, Pozzi Federico Emanuele, Agosta Federica, Ferini-Strambi Luigi, Filippi Massimo, Salsone Maria
Vita-Salute San Raffaele University, 20132 Milan, Italy.
IRCCS Policlinico San Donato, San Donato Milanese, 20097 Italy.
Sleep. 2025 Jun 20. doi: 10.1093/sleep/zsaf174.
Isolated rapid eye movement sleep (REM) behavior disorder (iRBD) represents the strongest predictor of α-synucleinopathies, with over 90% of patients developing Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy after a decade. As such, iRBD provides a critical window for early diagnosis and intervention. While molecular imaging techniques have been widely explored as powerful biomarkers for early disease detection, validated, more accessible tests based on biospecimens capable of reliably predicting phenoconversion remain lacking, creating a crucial gap in the clinical management of at-risk individuals. This review provides a critical overview of the latest findings in biofluid and tissue-based biomarkers in iRBD, emphasizing the most promising candidates and outlining key directions for future research and clinical applications. While cerebrospinal fluid (CSF)-based α-synuclein has widely proven high diagnostic and prognostic accuracy, blood, urine, stool, skin, olfactory, and oral mucosa samples offer a feasible approach for scalable, population-level screenings in prodromal α-synucleinopathies. The development of multimodal biomarker panels combining accessible biofluids and tissue samples may pave the way for early intervention and more effective risk stratification in future neuroprotective trials for α-synucleinopathies.
孤立性快速眼动睡眠行为障碍（iRBD）是α-突触核蛋白病最强的预测指标，超过90%的患者在十年后会发展为帕金森病、路易体痴呆或多系统萎缩。因此，iRBD为早期诊断和干预提供了关键窗口。虽然分子成像技术已被广泛探索作为早期疾病检测的强大生物标志物，但基于生物样本的经过验证且更易获取的能够可靠预测表型转化的检测方法仍然缺乏，这在高危个体的临床管理中造成了关键差距。本综述对iRBD中基于生物流体和组织的生物标志物的最新研究结果进行了批判性概述，强调了最有前景的候选标志物，并概述了未来研究和临床应用的关键方向。虽然基于脑脊液（CSF）的α-突触核蛋白已被广泛证明具有较高的诊断和预后准确性，但血液、尿液、粪便、皮肤、嗅觉和口腔黏膜样本为前驱性α-突触核蛋白病的可扩展人群水平筛查提供了一种可行的方法。结合易获取的生物流体和组织样本的多模态生物标志物组合的开发可能为未来α-突触核蛋白病神经保护试验中的早期干预和更有效的风险分层铺平道路。
