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Objective <p>This systematic review and meta-analysis evaluated the diagnostic performance of skin α-synuclein (α-syn) assays, focusing on key detection techniques.</p> Methods <p>A comprehensive search of PubMed, Web of Science, Embase, and Cochrane Library was conducted on April 6, 2024. Bivariate mixed-effects models were used to calculate pooled sensitivity and specificity with 95% confidence intervals (CIs) for each group and subgroup.</p> Results <p>In distinguishing Parkinson’s disease (PD) from healthy controls (HCs) or non-neurodegenerative controls (NNCs), overall sensitivity and specificity were 0.78 (95% CI 0.75–0.80) and 0.96 (95% CI 0.94–0.97), with seed amplification assays (SAA) showing the highest sensitivity (0.89, 95% CI 0.85–0.93) compared to immunofluorescence (IF) (0.82, 95% CI 0.78–0.85) and immunohistochemistry (IHC) (0.70, 95% CI 0.66–0.74). For differentiating PD from multiple system atrophy (MSA), sensitivity remained high (0.80, 95% CI 0.76–0.83), but specificity was low (0.25, 95% CI 0.20–0.31); SAA, IF and IHC all obtained low pooled specificities (less than 0.3). Discriminating from tauopathies, the pooled sensitivity and specificity were 0.82 (95% CI 0.77–0.86) and 0.88 (95% CI 0.81–0.92), with immunological methods using phosphorylated α-synuclein (p-α-syn) outperforming those using non-phosphorylated α-synuclein (np-α-syn); SAA had a higher sensitivity than immunology techniques.</p> Interpretation <p>Skin α-syn assays, particularly SAA and p-α-syn immunological methods, demonstrate strong potential as diagnostic tools for PD; SAA had a higher sensitivity than immunology techniques. However, distinguishing PD from other α-synucleinopathies is still challenging and variability across methods highlight the need for standardization. Further research should focus on integrating skin α-syn detection with other biomarkers to enhance diagnostic precision.</p>

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Skin α-synuclein assays in diagnosing Parkinson’s disease: a systematic review and meta-analysis

  • 期刊论文

  • 发表日期：

    2025年4月9日

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  • Yang Zhao,
  • Mingyue Luan,
  • Jing Liu,
  • Qingqing Wang,
  • Jianwen Deng,
  • Zhaoxia Wang,
  • Yunchuang Sun,
  • Kai Li

摘要

Objective

This systematic review and meta-analysis evaluated the diagnostic performance of skin α-synuclein (α-syn) assays, focusing on key detection techniques.

Methods

A comprehensive search of PubMed, Web of Science, Embase, and Cochrane Library was conducted on April 6, 2024. Bivariate mixed-effects models were used to calculate pooled sensitivity and specificity with 95% confidence intervals (CIs) for each group and subgroup.

Results

In distinguishing Parkinson’s disease (PD) from healthy controls (HCs) or non-neurodegenerative controls (NNCs), overall sensitivity and specificity were 0.78 (95% CI 0.75–0.80) and 0.96 (95% CI 0.94–0.97), with seed amplification assays (SAA) showing the highest sensitivity (0.89, 95% CI 0.85–0.93) compared to immunofluorescence (IF) (0.82, 95% CI 0.78–0.85) and immunohistochemistry (IHC) (0.70, 95% CI 0.66–0.74). For differentiating PD from multiple system atrophy (MSA), sensitivity remained high (0.80, 95% CI 0.76–0.83), but specificity was low (0.25, 95% CI 0.20–0.31); SAA, IF and IHC all obtained low pooled specificities (less than 0.3). Discriminating from tauopathies, the pooled sensitivity and specificity were 0.82 (95% CI 0.77–0.86) and 0.88 (95% CI 0.81–0.92), with immunological methods using phosphorylated α-synuclein (p-α-syn) outperforming those using non-phosphorylated α-synuclein (np-α-syn); SAA had a higher sensitivity than immunology techniques.

Interpretation

Skin α-syn assays, particularly SAA and p-α-syn immunological methods, demonstrate strong potential as diagnostic tools for PD; SAA had a higher sensitivity than immunology techniques. However, distinguishing PD from other α-synucleinopathies is still challenging and variability across methods highlight the need for standardization. Further research should focus on integrating skin α-syn detection with other biomarkers to enhance diagnostic precision.