The potential of phosphorylated α-synuclein as a biomarker for the diagnosis and monitoring of multiple system atrophy

Toufik Abdul-Rahman*, Ranferi Eduardo Herrera-Calderón, Arjun Ahluwalia, Andrew Awuah Wireko, Tomas Ferreira, Joecelyn Kirani Tan, Maximillian Wolfson, Shankhaneel Ghosh, Viktoriia Horbas, Vandana Garg, Asma Perveen, Marios Papadakis*, Ghulam Md Ashraf, Athanasios Alexiou*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

1 Citation (Scopus)

Abstract

Introduction: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder characterized by the presence of glial cytoplasmic inclusions (GCIs) containing aggregated α-synuclein (α-Syn). Accurate diagnosis and monitoring of MSA present significant challenges, which can lead to potential misdiagnosis and inappropriate treatment. Biomarkers play a crucial role in improving the accuracy of MSA diagnosis, and phosphorylated α-synuclein (p-syn) has emerged as a promising biomarker for aiding in diagnosis and disease monitoring. Methods: A literature search was conducted on PubMed, Scopus, and Google Scholar using specific keywords and MeSH terms without imposing a time limit. Inclusion criteria comprised various study designs including experimental studies, case-control studies, and cohort studies published only in English, while conference abstracts and unpublished sources were excluded. Results: Increased levels of p-syn have been observed in various samples from MSA patients, such as red blood cells, cerebrospinal fluid, oral mucosal cells, skin, and colon biopsies, highlighting their diagnostic potential. The α-Syn RT-QuIC assay has shown sensitivity in diagnosing MSA and tracking its progression. Meta-analyses and multicenter investigations have confirmed the diagnostic value of p-syn in cerebrospinal fluid, demonstrating high specificity and sensitivity in distinguishing MSA from other neurodegenerative diseases. Moreover, combining p-syn with other biomarkers has further improved the diagnostic accuracy of MSA. Conclusion: The p-syn stands out as a promising biomarker for MSA. It is found in oligodendrocytes and shows a correlation with disease severity and progression. However, further research and validation studies are necessary to establish p-syn as a reliable biomarker for MSA. If proven, p-syn could significantly contribute to early diagnosis, disease monitoring, and assessing treatment response.

Original languageEnglish
Article numbere14678
JournalCNS Neuroscience and Therapeutics
Volume30
Issue number4
DOIs
Publication statusPublished - Apr 2024
Externally publishedYes

Keywords

  • biomarker
  • diagnosis
  • multiple system atrophy
  • phosphorylated α-synuclein

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