There is a dire need for reliable biomarkers to solidify an early and accurate diagnosis of multiple system atrophy (MSA). We sought to compare the ability of emerging plasma markers in distinguishing MSA from its mimics and healthy controls in early disease stages, and to evaluate their performance in detecting disease severity and brain atrophy. Plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), phosphorylated tau181, amyloid-β (Aβ)42, and Aβ40 were measured using ultrasensitive Simoa in early-stage patients with MSA (n = 73), spinocerebellar ataxia (SCA, n = 29), Parkinson’s disease (PD, n = 28), and healthy controls (n = 100). We observed that elevated NfL outperformed other biomarkers in distinguishing MSA and its subtypes (AUC = 0.9) versus controls. Intriguingly, when separating MSA from its mimics, increased GFAP (AUC = 0.717) in MSA-C and decreased Aβ40 (AUC = 0.807) in MSA-P best discriminated from SCA and PD respectively. Plasma levels were comparable between MSA-C and MSA-P and the differentiation by plasma index alone was poor. Combining plasma markers noticeably improved the discriminatory efficacy. Of note, among MSA patients, higher GFAP and NfL were correlated with the atrophy of brain regions vulnerable to MSA (e.g., cerebellum, pons, or putamen). They could also aggravate the severity of MSA, and this association was partially mediated by cerebral volumes. In contrast, no obvious associations of phosphorylated tau and Aβ with disease severity were observed. Collectively, plasma biomarkers, especially in combination, are useful to facilitate the discriminatory work-up of MSA at early stages. Moreover, NfL and GFAP may be promising biomarkers to monitor the disease severity of MSA.

迫切需要可靠的生物标志物来巩固对多系统萎缩 (MSA) 的早期和准确诊断。我们试图比较新兴血浆标志物在早期疾病阶段将 MSA 与其模拟物和健康对照区分开来的能力，并评估它们在检测疾病严重程度和脑萎缩方面的表现。使用超灵敏 Simoa 对早期 MSA（n = 73）、脊髓小脑性共济失调（  SCA , n  = 29), 帕金森病 (PD, n  = 28), 和健康对照 ( n = 100）。我们观察到，升高的 NfL 在区分 MSA 及其亚型 (AUC = 0.9) 与对照方面优于其他生物标志物。有趣的是，当将 MSA 与其模拟物分离时，MSA-C 中的 GFAP (AUC = 0.717) 增加，MSA-P 中的 Aβ40 (AUC = 0.807) 减少，这与 SCA 和 PD 的区别最好。MSA-C 和 MSA-P 之间的血浆水平相当，仅通过血浆指数进行区分很差。结合血浆标记显着提高了辨别效力。值得注意的是，在 MSA 患者中，较高的 GFAP 和 NfL 与易受 MSA 影响的大脑区域（例如，小脑、脑桥或壳核）萎缩相关。它们还可能加重 MSA 的严重程度，并且这种关联部分由脑容量介导。相比之下，未观察到磷酸化 tau 和 Aβ 与疾病严重程度的明显关联。总的来说，血浆生物标志物，尤其是联合使用，有助于在早期阶段对 MSA 进行区分性检查。此外，NfL 和 GFAP 可能是监测 MSA 疾病严重程度的有前途的生物标志物。