Evaluating Dynamic Light Scattering for α-Synuclein Oligomer Analysis in Cerebrospinal Fluid
Aleksandr Shefer1, Mariia S. Kuzmina1, Stanislav O. Yurchenko1, Anastasia A. Belyaeva1;
1Centre for Soft Matter and Physics of Fluids, Bauman Moscow State Technical University, 2nd Baumanskaya street 5, 105005 Moscow, Russia
Abstract
Oligomeric forms of α-synuclein are biomarkers of neurodegenerative disorders, but their low abundance in cerebrospinal fluid (CSF) substantially limits direct analytical characterization. Preliminary enrichment may improve their detectability; however, separation procedures can alter protein size distributions or induce nonspecific aggregation. Reliable analytical tools are therefore required to distinguish true enrichment of α-synuclein oligomers from artifacts introduced during sample processing.
Here, we evaluate conventional dynamic light scattering (DLS) as a rapid comparative method for analyzing CSF and CSF-like protein systems containing oligomeric α-synuclein. Model solutions were developed to assess the contributions of electrolyte composition, major CSF proteins, and particle populations mimicking oligomeric and aggregated species to the measured DLS signal. Particular attention was paid to physiologically relevant concentrations, measurement reproducibility and interpretation of multimodal size distributions.
The effects of protein composition, thermal treatment and filtration on particle-size distributions were further examined to identify factors that may complicate the analysis of native and enriched CSF samples. The results highlight the strong contribution of large particles and aggregates to the DLS signal, indicating that shifts in apparent size distributions cannot alone confirm enrichment of α-synuclein oligomers.
The proposed approach provides a framework for using DLS as a screening and quality-control tool during optimization of α-synuclein oligomer enrichment protocols, helping to identify nonspecific aggregation, sample destabilization, and major changes in particle populations.
The research was financially supported by the Ministry of Science and Higher Education of the Russian Federation (Agreement on the provision from the federal budget of a grant in the form of subsidies for state support of development programs for world-class research centers carrying out research and development in priority areas of scientific and technological development dated June 3, 2026, No. 075-15-2026-383)
Speaker
Aleksandr Shefer
Centre for Soft Matter and Physics of Fluids, Bauman Moscow State Technical University
Russia
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