Mass Spectrometric Analysis of Cerebrospinal Fluid Ubiquitin in Alzheimer's Disease and Parkinsonian Disorders

Research output: Contribution to journalArticle

Abstract

Purpose: Dysfunctional proteostasis, with decreased protein degradation and an accumulation of ubiquitin into aggregated protein inclusions, is a feature of neurodegenerative diseases. Identifying new potential biomarkers in cerebrospinal fluid (CSF) reflecting this process could contribute important information on pathophysiology. Experimental design: A developed method combining SPE and PRM-MS is employed to monitor the concentration of ubiquitin in CSF from subjects with Alzheimer's disease (AD), Parkinson's disease (PD), and progressive supranuclear palsy (PSP). Four independent cross-sectional studies are conducted, studies 1–4, including controls (n = 86) and participants with AD (n = 60), PD (n = 15), and PSP (n = 11). Results: The method shows a repeatability and intermediate precision not exceeding 6.1 and 7.9%, respectively. The determined LOD is 0.1 nm and the LOQ range between 0.625 and 80 nm. The CSF ubiquitin concentration is 1.2–1.5-fold higher in AD patients compared with controls in the three independent AD-control studies (Study 1, p < 0.001; Study 2, p < 0.001; and Study 3, p = 0.003). In the fourth study, there is no difference in PD or PSP, compared to controls. Conclusion and clinical relevance: CSF ubiquitin may reflect dysfunctional proteostasis in AD. The described method can be used for further exploration of ubiquitin as a potential biomarker in neurodegenerative diseases.

Details

Authors
  • Simon Sjödin
  • Oskar Hansson
  • Annika Öhrfelt
  • Gunnar Brinkmalm
  • Henrik Zetterberg
  • Ann Brinkmalm
  • Kaj Blennow
Organisations
External organisations
  • Skåne University Hospital
  • Sahlgrenska University Hospital
  • University College London
  • University of Gothenburg
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology

Keywords

  • alzheimer's disease, biomarker, parkinson's disease, progressive supranuclear palsy, ubiquitin
Original languageEnglish
Article number1700100
JournalProteomics - Clinical Applications
Volume11
Issue number11-12
StatePublished - 2017 Dec 1
Peer-reviewedYes