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CSF alpha-Synuclein Seed Amplification Assay results in routine clinically collected samples.

Elisabeth Dinter1,2, Julia L Margraff1, Iñaki Schniewind1,2

  • 1Department of Neurology, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany.

Journal of Parkinson'S Disease
|April 7, 2026
PubMed
Summary

The alpha-synuclein-Seed Amplification Assay (αSyn-SAA) in cerebrospinal fluid shows high accuracy for diagnosing Lewy body diseases in clinical settings. This test holds promise for routine clinical use in identifying neurodegenerative conditions.

Keywords:
Lewy body pathologyalpha-synucleinbiological definitionneuronal synuclein diseasesseed amplification assay

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Area of Science:

  • Neurology
  • Biochemistry
  • Diagnostic Medicine

Background:

  • Lewy body pathology is detectable via alpha-synuclein-Seed Amplification Assay (αSyn-SAA) in cerebrospinal fluid (CSF) with high accuracy in research cohorts.
  • The performance of αSyn-SAA in CSF samples from routine clinical practice, outside of controlled cohort studies, is not well understood.

Purpose of the Study:

  • To assess the agreement between αSyn-SAA results in CSF and clinical diagnoses in patients encountered in routine clinical practice.
  • To evaluate the diagnostic utility of αSyn-SAA in a diverse patient population with various neurological and psychiatric conditions.

Main Methods:

  • A cross-sectional study involving 356 participants undergoing lumbar puncture for diagnostic or therapeutic reasons.
  • Cerebrospinal fluid samples were analyzed using αSyn-SAA.
  • Data included binary αSyn-SAA results, neurological examination findings, and structured medical history.

Main Results:

  • αSyn-SAA was positive in all tested samples from patients diagnosed with Parkinson's disease (PD), dementia with Lewy bodies (DLB), and pure autonomic failure.
  • The assay also detected αSyn-SAA in subsets of patients with Alzheimer's disease and normal pressure hydrocephalus.
  • Results demonstrated high concordance between αSyn-SAA findings and clinical diagnoses for PD and DLB.

Conclusions:

  • αSyn-SAA in CSF exhibits high concordance with clinical diagnoses of PD and DLB, similar to findings in cohort studies.
  • These results support the potential diagnostic value of αSyn-SAA for routine clinical application.
  • The assay's ability to detect Lewy body co-pathology across various neurodegenerative diseases presents both opportunities and challenges for interpretation.