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Background <p>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.</p> Methods <p>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.</p> Results <p>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).</p> Conclusions <p>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.</p>

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CSF phospho-tau levels at Parkinson’s disease onset predict the risk for development of motor complications

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月13日

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  • Jacopo Bissacco,
  • Giulia Di Lazzaro,
  • Roberta Bovenzi,
  • Giulia Maria Sancesario,
  • Matteo Conti,
  • Clara Simonetta,
  • Davide Mascioli,
  • Maria Mancini,
  • Veronica Buttarazzi,
  • Mariangela Pierantozzi,
  • Massimo Pieri,
  • Sergio Bernardini,
  • Alessandro Stefani,
  • Anna Rita Bentivoglio,
  • Paolo Calabresi,
  • Nicola Biagio Mercuri,
  • Tommaso Schirinzi

摘要

Background

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.

Methods

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.

Results

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).

Conclusions

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.