Dysregulated Cerebrospinal Fluid Proteome of Spinocerebellar Ataxia Type 2 and its Clinical Implications

Mov Disord. 2024 Aug;39(8):1418-1423. doi: 10.1002/mds.29834. Epub 2024 May 20.

Abstract

Background: Abnormalities in ataxin-2 associated with spinocerebellar ataxia type 2 (SCA2) may lead to widespread disruptions in the proteome. This study was performed to identify dysregulated proteome in SCA2 and to explore its clinical-radiological correlations.

Methods: Cerebrospinal fluid (CSF) samples from 21 genetically confirmed SCA2 were subjected to shotgun proteome analysis using mass spectrometry (MS) and tandem mass tag (TMT)-based multiplexing. Proteins with at least 1.5-fold change in abundance were identified. Their relative abundance was measured using parallel reaction monitoring (PRM) and correlated against disease-related factors.

Results: Eleven proteins were significantly upregulated in SCA2. They belonged to the family of cell adhesion molecules and granins. Their fold changes showed significant clinical, genetic, and radiological correlations.

Conclusions: Significant dysregulation of CSF proteome is seen in SCA2. The dysregulated protein may have potential use in clinical evaluation of patients with SCA2.

Keywords: MRI; cerebrospinal fluid; proteomics; spinocerebellar ataxia type 2.

MeSH terms

  • Adult
  • Aged
  • Ataxin-2 / cerebrospinal fluid
  • Ataxin-2 / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Proteome*
  • Spinocerebellar Ataxias* / cerebrospinal fluid
  • Spinocerebellar Ataxias* / genetics

Substances

  • Proteome
  • Ataxin-2
  • ATXN2 protein, human