Objective: To evaluate the diagnostic performance of alpha-synuclein (a-syn) seeding amplification assays (SAA) in skin and tear fluid (TF) as non-invasive alternatives to cerebrospinal fluid (CSF) for Parkinson’s disease (PD).

Background: Parkinson’s disease is defined by pathological α-syn aggregation [2]. While CSF a-syn SAA is considered the “gold standard,” invasive lumbar punctures impede adoption and monitoring [1], [3]. Cutaneous and ocular biofluids are accessible matrices that reveal early pathology [4]. Validating these tools makes Parkinson’s disease diagnostics more accessible in clinical practice [4], [5].

Method: We assessed diagnostic accuracy using multi-center cohorts and network meta-analyses of a-syn SAA in TF and skin [1], [4]. The primary outcomes included sensitivity, specificity, and agreement (Cohen’s kappa, κ) versus clinical diagnosis or CSF [3]. Studies utilizing real-time quaking-induced conversion (RT-QuIC) or streamlined protocols (e.g., 50°C incubation) were prioritized [2], [5].

Results: Cutaneous a-syn SAA had an accuracy rate ranging from 88.9% to 96% [1], [3], [5]. The agreement between skin and CSF SAA was almost perfect (κ = 0.86) [3]. In rapid 24-hour protocols [5], the C7 cervical region showed higher sensitivity (92.46%) and specificity (93.33%). There was a significant correlation (p < 0.05) between cutaneous seeding activity, disease duration, and Hoehn and Yahr stage [5]. In ocular matrices, a-syn SAA distinguished PD from controls with a positivity rate of over 55% [4] (see Table 1). Although TF reactions had slower kinetics and a lower maximum fluorescence than CSF, the results were consistent across all subjects [4]. TF offers a contamination-free environment for studying early brainstem innervation [4]. According to a meta-analysis, skin SAA sensitivity is 0.91, similar to CSF (0.89) [1] (see Figure 1).

Conclusion: Cutaneous a-syn SAA has comparable accuracy to CSF testing, confirming its role as a validated, minimally invasive biomarker [1], [3]. While TF SAA requires further optimization, it is a promising non-invasive screening platform [2], [4]. Replacing spinal taps with these biofluids has the potential to transform Parkinson’s disease management by allowing for earlier diagnosis and scalable longitudinal monitoring [2, 3].

in Result section “.. rate exceeding 55%”

at the most end of Result section.

References: [1] Rissardo JP, Fornari Caprara AL. Alpha-Synuclein Seed Amplification Assays in Parkinson’s Disease: A Systematic Review and Network Meta-Analysis. Clin Pract. 2025; 15(6):107. doi:10.3390/clinpract15060107
[2] Donadio V, Ingelsson M, Rizzo G, et al. Diagnostic biomarkers for α-synucleinopathies—state of the art and future developments: a systematic review. Mol Neurodegeneration. 2025. doi:10.1186/s13024-025-00914-0
[3] Bsoul R, McWilliam OH, Waldemar G, et al. Accurate detection of pathologic α-synuclein in CSF, skin, olfactory mucosa, and urine with a uniform seeding amplification assay. Acta Neuropathol Commun. 2025; 13:113. doi:10.1186/s40478-025-02034-8
[4] Canaslan S, Schmitz M, Maass F, et al. Detection of alpha synuclein seeding activity in tear fluid in patients with Parkinson’s disease. bioRxiv. 2025. doi:10.1101/2025.01.16.633314
[5] Kuang Y, Mao H, Gan T, et al. A skin-specific α-Synuclein seeding amplification assay for diagnosing Parkinson’s disease. npj Parkinsons Dis. 2024;10:129. doi:10.1038/s41531-024-00738-7.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/beyond-the-spinal-tap-diagnostic-accuracy-of-alpha-synuclein-seeding-amplification-assays-saa-in-cutaneous-and-ocular-biofluids-a-comparative-diagnostic-accuracy-review/