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Proteomics Clin Appl. 2017 Dec;11(11-12). doi: 10.1002/prca.201700100. Epub 2017 Nov 2.

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

Author information

1
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
2
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
3
Memory Clinic, Skåne University Hospital, Malmö, Sweden.
4
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
5
Department of Molecular Neuroscience, University College London Institute of Neurology, London, UK.
6
UK Dementia Research Institute at UCL, London, UK.

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.

KEYWORDS:

alzheimer's disease; biomarker; parkinson's disease; progressive supranuclear palsy; ubiquitin

PMID:
28972305
PMCID:
PMC5765402
DOI:
10.1002/prca.201700100
[Indexed for MEDLINE]
Free PMC Article

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