Bissacco Jacopo, Di Lazzaro Giulia, Bovenzi Roberta, Sancesario Giulia Maria, Conti Matteo, Simonetta Clara, Mascioli Davide, Mancini Maria, Buttarazzi Veronica, Pierantozzi Mariangela, Pieri Massimo, Bernardini Sergio, Stefani Alessandro, Bentivoglio Anna Rita, Calabresi Paolo, Mercuri Nicola Biagio, Schirinzi Tommaso
Department of Systems Medicine, University of Rome "Tor Vergata", Via Montpellier, 00133, Rome, Italy.
Institute of Neurology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
J Neurol. 2025 Aug 13;272(9):573. doi: 10.1007/s00415-025-13325-4.
Motor complications (MC), including fluctuations, represent a disabling milestone of Parkinson's disease (PD) course, although the underlying early pathophysiological mechanisms remain unclear. We therefore investigated whether the biological profile at PD onset, as defined through a panel of CSF biomarkers, may predispose to the development of MC.
We conducted a dual-center retrospective longitudinal study involving 131 de novo (DN) PD patients (newly diagnosed, untreated). At baseline, patients were evaluated by motor and non-motor scores, and the measurement of CSF total α-synuclein (α-syn), total and phosphorylated-181-tau (t-tau, p-tau), amyloid-β42 and amyloid-β40 (Aβ42, Aβ40) levels, p-tau/t-tau, Aβ42/Aβ40, and p-tau/Aβ42 ratios. According to the successive development of MC, patients were classified as "with MC" (wMC) or "without MC" (noMC). A control group of 107 controls was also collected. Variables were compared between groups, adjusting for main covariates; ROC and Cox analyses evaluated predictive values.
The DN PD cohort was followed for 57 (± 18) months, with 38 (29%) patients developing MC. At baseline, DN patients showed lower CSF total α-syn and t-tau levels than controls. The wMC group had higher p-tau, p-tau/t-tau, and p-tau/Aβ42 ratios than noMC. The p-tau/t-tau ratio best predicted MC development; above the cutoff of 0.148, MC were 2.6 times more likely with 81% sensitivity and 61% specificity (AUC = 0.79).
Elevated CSF p-tau/t-tau ratio in DN PD patients predicts higher MC risk, supporting biomarker-based stratification for patients at onset. Our findings also highlight Alzheimer's co-pathology, especially tauopathy, as a key factor in shaping PD motor progression from early stages.
运动并发症（MC），包括症状波动，是帕金森病（PD）病程中的一个致残性阶段，尽管其潜在的早期病理生理机制仍不清楚。因此，我们研究了通过一组脑脊液生物标志物定义的PD发病时的生物学特征是否易导致MC的发生。
我们进行了一项双中心回顾性纵向研究，纳入131例初发（DN）PD患者（新诊断、未治疗）。在基线时，通过运动和非运动评分以及测量脑脊液中总α-突触核蛋白（α-syn）、总tau蛋白和磷酸化-181-tau蛋白（t-tau、p-tau）、淀粉样蛋白-β42和淀粉样蛋白-β40（Aβ42、Aβ40）水平、p-tau/t-tau、Aβ42/Aβ40和p-tau/Aβ42比值对患者进行评估。根据MC的后续发展情况，将患者分为“有MC”（wMC）或“无MC”（noMC）。还收集了107名对照组成的对照组。对组间变量进行比较，并对主要协变量进行校正；ROC和Cox分析评估预测价值。
DN PD队列随访了57（±18）个月，有38例（29%）患者出现MC。在基线时，DN患者脑脊液中总α-syn和t-tau水平低于对照组。wMC组的p-tau、p-tau/t-tau和p-tau/Aβ42比值高于noMC组。p-tau/t-tau比值最能预测MC的发生；高于0.148的临界值时，发生MC的可能性增加2.6倍。敏感性为81%，特异性为61%（AUC = 0.79）。
DN PD患者脑脊液中p-tau/t-tau比值升高预示着MC风险更高，支持对发病时的患者进行基于生物标志物的分层。我们的研究结果还强调了阿尔茨海默病共病，尤其是tau蛋白病，是影响PD早期运动进展的关键因素。
