REVIEW: Diagnostics of Synucleinopathies by Protein Amplification Methods: Methodological and Bibliometric Analysis

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Alexander A. Groshkov^1,a*, Nataliya A. Kolotyeva¹, Pavel P. Tregub^1,2, Victoria I. Zhdankina¹, Yulia K. Komleva¹, Alla B. Salmina¹, and Sergey N. Illarioshkin¹

¹Russian Center of Neurology and Neurosciences, 125367 Moscow, Russia

²Scientific and Educational Resource Center for Innovative Technologies of Immunophenotyping, Digital Spatial Profiling, and Ultrastructural Analysis, People’s Friendship University, 117198 Moscow, Russia

^* To whom correspondence should be addressed.

Received: July 14, 2025; Revised: November 19, 2025; Accepted: November 20, 2025

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Early preclinical diagnostics of neurodegenerative diseases (synucleinopathies, Alzheimer’s disease, etc.) can be achieved through the detection of pathological amyloid aggregates in biological fluids. Protein amplification methods (PMCA, RT-QuIC) have become promising diagnostic tools by offering high sensitivity and specificity for detecting α-synuclein oligomers at the early disease stages and studying the fibril formation kinetics and mechanisms of amyloid aggregation. However, these methods have several significant limitations, as they are technically complex and time-consuming and lack standardized protocols, control samples, and substrates. Despite these challenges, protein amplification methods hold potential as the most productive, accessible, and standardizable diagnostic approaches in synucleinopathies. This review presents the results of bibliometric analysis of publications on the use of protein amplification methods in the diagnostics of synucleinopathies. We also provide a comparative analysis of common RT-QuIC protocols, with special focus on the method principles, approaches for its optimization, types of biological materials, key factors influencing the sensitivity and specificity of this technique, and areas for its improvement.

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KEY WORDS: protein amplification, RT-QuIC, PMCA, neurodegenerative diseases, synucleinopathies, α-synuclein, fibrillization, early diagnostics, cerebrospinal fluid, bibliometric analysis, Parkinson’s disease, dementia with Lewy bodies, multiple system atrophy

DOI: 10.1134/S000629792560214X

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