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<p>Parkinson’s disease (PD) is a clinically heterogeneous neurodegenerative disorder characterized by intraneuronal accumulation of misfolded α-synuclein. Real-time quaking-induced conversion (RT-QuIC) detects seeding-competent αSyn species but commonly relies on invasive matrices. We evaluated tear fluid (TF) as a non-invasive biofluid for αSyn RT-QuIC in 44 PD patients and 32 matched healthy controls (HCs). ROC analyses were performed on participant-level readouts (mean of four technical replicates), and optimal cut-offs were selected using the Youden index before being applied to each technical replicate. At the subject level, the best trade-offs were observed at maximum fluorescence (MaxRFU) ≥ 2/4 (sensitivity 59.1%; specificity 65.6%), MedianRFU ≥ 3/4 (sensitivity 40.9%; specificity 78.1%), and area under fluorescence curve (AUFC) ≥ 3/4 (sensitivity 47.7%; specificity 71.9%). In a sensitivity analysis excluding RT-QuIC positive HCs with potential prodromal/risk features, specificity increased to 75% (MaxRFU), 86.2% (MedianRFU), and 79.3% (AUFC). Assay-characterization analyses, performed including all technical replicates, showed significantly higher fluorescence signals throughout the RT-QuIC amplification curve (<i>p</i> &lt; 0.0001) with shorter lag phase, higher MedianRFU and MaxRFU, and larger AUFC values in PD than in HCs (all <i>p</i> &lt; 0.05). Exploratory subgroup analyses suggested possible phenotype-related variability in test response. Our findings suggest that αSyn seeding activity may be detected in TF. Despite suboptimal sensitivity, non-invasiveness and promising specificity support further optimization of TF-based RT-QuIC as a diagnostic tool for synucleinopathies.</p>

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Tear fluid as a novel specimen for detection of alpha-synuclein seeding activity in Parkinson’s disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月10日

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  • Matteo Costanzo,
  • Anna Ladogana,
  • Marco Sbriccoli,
  • Francesco Marchet,
  • Flavia Porreca,
  • Clara Salciccia,
  • Michele Equestre,
  • Gabriele Moracci,
  • Maria Ilenia De Bartolo,
  • Giulia Ruocco,
  • Filippo Carlo Carlà,
  • Antonella Conte,
  • Giovanni Fabbrini,
  • Daniele Belvisi,
  • Anna Poleggi

摘要

Parkinson’s disease (PD) is a clinically heterogeneous neurodegenerative disorder characterized by intraneuronal accumulation of misfolded α-synuclein. Real-time quaking-induced conversion (RT-QuIC) detects seeding-competent αSyn species but commonly relies on invasive matrices. We evaluated tear fluid (TF) as a non-invasive biofluid for αSyn RT-QuIC in 44 PD patients and 32 matched healthy controls (HCs). ROC analyses were performed on participant-level readouts (mean of four technical replicates), and optimal cut-offs were selected using the Youden index before being applied to each technical replicate. At the subject level, the best trade-offs were observed at maximum fluorescence (MaxRFU) ≥ 2/4 (sensitivity 59.1%; specificity 65.6%), MedianRFU ≥ 3/4 (sensitivity 40.9%; specificity 78.1%), and area under fluorescence curve (AUFC) ≥ 3/4 (sensitivity 47.7%; specificity 71.9%). In a sensitivity analysis excluding RT-QuIC positive HCs with potential prodromal/risk features, specificity increased to 75% (MaxRFU), 86.2% (MedianRFU), and 79.3% (AUFC). Assay-characterization analyses, performed including all technical replicates, showed significantly higher fluorescence signals throughout the RT-QuIC amplification curve (p < 0.0001) with shorter lag phase, higher MedianRFU and MaxRFU, and larger AUFC values in PD than in HCs (all p < 0.05). Exploratory subgroup analyses suggested possible phenotype-related variability in test response. Our findings suggest that αSyn seeding activity may be detected in TF. Despite suboptimal sensitivity, non-invasiveness and promising specificity support further optimization of TF-based RT-QuIC as a diagnostic tool for synucleinopathies.