Quantitative Determination of Alpha-Synuclein in Parkinson’s Disease

Ligand Binding (Immunoassays)

Background


Alpha-Synuclein (α‑synuclein) is the principal component of Lewy bodies and neurites—the pathological hallmark of Parkinson’s Disease (PD). Aggregation and misfolding of alpha-synuclein drive neuronal dysfunction and degeneration. Aberrant alpha-synuclein pathology and Lewy bodies are characteristic of several neurological conditions known as “synucleinopathies” including Parkinson’s Disease, Lewy Body Dementia, and Multiple System Atrophy. Measuring total alpha-synuclein levels in cerebrospinal fluid (CSF) provides essential insights into pharmacodynamics and disease progression in investigational clinical trials.
 

Overview
  • Assay Name: Quantitative Determination of Alpha-Synuclein in Human CSF
  • Validation Level: IDE/IVDR Compliant
  • Assay Type: Electrochemiluminescence
  • Intended Use: Pharmacodynamic monitoring as primary, secondary, or exploratory endpoints in clinical trials
     

Clinical Utility
 

Designed to quantify directional change in CSF alpha-synuclein in response to investigational agents, this assay is ideal for:
 

  • Assessing the impact of disease-modifying therapies (e.g., siRNAs targeting alpha-synuclein expression)
  • Enhancing confidence in therapeutic development for Parkinson’s Disease and related disorders
     

Validation Summary


This fit-for-purpose immunoassay was validated per FDA Bioanalytical Method Validation and Clinical & Laboratory Standards Institute (CLSI) guidelines with the following key validation parameters:
 

  • Precision & Accuracy
  • Limit of Quantification (LoQ)
  • Selectivity & Specificity
  • Specimen Stability with Freeze/Thaw Cycling
  • Interference Testing
  • Dilution Linearity
  • Limit of Blank (LoB)
  • Prozone (Hook Effect)
  • Limit of Detection (LoD)
 

 

Figure 1: Alpha-Synuclein Assay Workflow & Key Specifications
Figure 1: Alpha-Synuclein Assay Workflow & Key Specifications

 

Sponsor Deliverables

  • CLIA-compliant reports with concentrations (pg/mL), quality flags & Rapid TAT
  • Lot and control summaries
  • Optional blinded data reviews
  • Optional statistical support for pharmacodynamic endpoint definition and sample‑size calculations
     

References

  • Eusebi P, et al. Diagnostic utility of CSF α‑synuclein in PD: A systematic review & meta‑analysis. Mov Disord. 2017;32:1389‑1400. doi: 10.1002/mds.27110. Epub 2017 Sep 7.
  • Xiang C, et al. A meta-analysis of the diagnostic utility of biomarkers in CSF in PD. npj Parkinson’s Disease 8, 165 (2022). https://doi.org/10.1038/s41531-022-00431-7.
  • Dutta S, et al. Development of a Novel Electrochemiluminescence ELISA for Quantification of α‑synuclein Phosphorylated at Ser129 in Biological Samples. ACS Chem Neurosci. 2023. doi: 10.1021/acschemneuro.2c00676.
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