Bombaci Alessandro, De Marco Giovanni, Casale Federico, Salamone Paolina, Marchese Giulia, Fuda Giuseppe, Calvo Andrea, Chiò Adriano
Turin ALS Centre, "Rita Levi Montalcini" Department of Neuroscience, University of Torino, Turin, Italy.
IRCSS Policlinico San Donato, San Donato, Milanese, Italy.
Eur J Neurol. 2025 Jun;32(6):e70241. doi: 10.1111/ene.70241.
Motor neuron diseases (MND) are heterogeneous and complex neurodegenerative disorders. Biomarkers could facilitate early diagnosis, prognosis determination, and patient stratification. Among the most studied biomarkers are neurofilaments, with peripherin (PRPH), a specific type predominantly expressed in the peripheral nervous system, gaining attention. To date, no studies have evaluated PRPH in human plasma.
Sandwich-ELISA was used to quantify plasma peripherin from 120 MND (100 ALS, 4 PMA, 15 PLS), 73 MND-mimics, and 38 healthy-controls (HCs). Plasma was collected at diagnosis or some months earlier. 41 ALS were evaluated longitudinally. ALSFRSr, MRC, spirometry, genetic tests, disease progression rate (PR), blood examinations, and neuropsychological tests were performed. Statistical analyses included Kruskal-Wallis, Mann-Whitney, Cox regression, and Kaplan-Meier curves.
Plasma PRPH levels differed significantly among groups (p < 0.0001), showing higher values in MND participants than MND mimics and HCs. Moreover, PRPH levels were elevated in PLS compared with HSP patients (p = 0.0001). Differences persisted after adjusting for age and sex. ROC curve demonstrated that PRPH discriminated MND from MND mimics (AUC = 0.85). Elevated PRPH correlated positively with ALSFRSr and lower motor neuron index, whereas inversely with disease progression rate. Higher PRPH levels at the beginning of the disease were associated with longer survival.
Plasma PRPH is raised in MND, particularly ALS, from the earliest stages, distinguishing MND from mimics and correlating with clinical parameters and survival. This suggests PRPH may reflect an endogenous response of lower motor neuron to injury. Further multicenter studies are required to refine the diagnostic and prognostic utility of PRPH in MND.
运动神经元病（MND）是异质性且复杂的神经退行性疾病。生物标志物有助于早期诊断、预后判定及患者分层。研究最多的生物标志物之一是神经丝，其中外周蛋白（PRPH），一种主要在外周神经系统表达的特定类型，受到了关注。迄今为止，尚无研究评估人血浆中的PRPH。
采用夹心酶联免疫吸附测定法（Sandwich-ELISA）对120例MND患者（100例肌萎缩侧索硬化症患者、4例进行性肌肉萎缩患者、15例原发性侧索硬化症患者）、73例MND疑似患者及38例健康对照者的血浆外周蛋白进行定量分析。血浆在诊断时或诊断前数月采集。对41例肌萎缩侧索硬化症患者进行了纵向评估。进行了肌萎缩侧索硬化功能评分修订版（ALSFRSr）、医学研究委员会（MRC）评分、肺活量测定、基因检测、疾病进展率（PR）、血液检查及神经心理学测试。统计分析包括Kruskal-Wallis检验、Mann-Whitney检验、Cox回归分析及Kaplan-Meier曲线分析。
各组间血浆PRPH水平差异显著（p < 0.0001），MND参与者的PRPH水平高于MND疑似患者和健康对照者。此外，与遗传性痉挛性截瘫（HSP）患者相比，原发性侧索硬化症患者的PRPH水平升高（p = 0.0001）。在对年龄和性别进行校正后，差异仍然存在。ROC曲线表明，PRPH可区分MND与MND疑似患者（曲线下面积[AUC] = 0.85）。PRPH升高与ALSFRSr及下运动神经元指数呈正相关，而与疾病进展率呈负相关。疾病初期较高的PRPH水平与较长的生存期相关。
MND患者，尤其是肌萎缩侧索硬化症患者，从疾病最早阶段开始血浆PRPH水平就会升高，这可将MND与疑似患者区分开来，并与临床参数及生存期相关。这表明PRPH可能反映了下运动神经元对损伤的内源性反应。需要进一步开展多中心研究以完善PRPH在MND中的诊断和预后效用。
