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Systematic Analysis of the Cerebrospinal Fluid Proteome of Fibromyalgia patients
(Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.)
(Department of Chemistry-BMC, Analytical Chemistry, Uppsala University, Uppsala, Sweden.)
(Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.)
(Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.)
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Fibromyalgia (FM) is a syndrome characterized by widespread muscular pain, fatigue and functional symptoms, which is known to be difficult to diagnose as the various symptoms overlap with many other conditions. Currently, there are no biomarkers for FM, and the diagnosis is made subjectively by the clinicians. We have performed shotgun proteomics on cerebrospinal fluid (CSF) from FM patients and non-pain controls to find potential biomarker candidates for this syndrome. Based on our multivariate and univariate analyses, we found that the relative differences in the CSF proteome between FM patients and controls were moderate. Four proteins, important to discriminate FM patients from non-pain controls, were found: Apolipoprotein C-III, Galectin-3-binding protein, Malate dehydrogenase cytoplasmic and the neuropeptide precursor protein ProSAAS. These proteins are involved in lipoprotein lipase (LPL) activity, inflammatory signaling, energy metabolism and neuropeptide signaling.

Keyword [en]
cerebrospinal fluid, biomarker, chronic pain, fibromyalgia, inflammation, neuroinflammation, mass spectrometry
National Category
Health Sciences Neurosciences Clinical Laboratory Medicine Biomedical Laboratory Science/Technology
Research subject
Bioinformatics; Biology with specialization in Molecular Biology; Chemistry with specialization in Analytical Chemistry; Medical Science; Clinical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-331615OAI: oai:DiVA.org:uu-331615DiVA: diva2:1149496
Available from: 2017-10-16 Created: 2017-10-16 Last updated: 2017-10-17
In thesis
1. Proteomics Studies of Subjects with Alzheimer’s Disease and Chronic Pain
Open this publication in new window or tab >>Proteomics Studies of Subjects with Alzheimer’s Disease and Chronic Pain
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Alzheimer’s disease (AD) is a neurodegenerative disease and the major cause of dementia, affecting more than 50 million people worldwide. Chronic pain is long-lasting, persistent pain that affects more than 1.5 billion of the world population. Overlapping and heterogenous symptoms of AD and chronic pain conditions complicate their diagnosis, emphasizing the need for more specific biomarkers to improve the diagnosis and understand the disease mechanisms.

To characterize disease pathology of AD, we measured the protein changes in the temporal neocortex region of the brain of AD subjects using mass spectrometry (MS). We found proteins involved in exo-endocytic and extracellular vesicle functions displaying altered levels in the AD brain, potentially resulting in neuronal dysfunction and cell death in AD.

To detect novel biomarkers for AD, we used MS to analyze cerebrospinal fluid (CSF) of AD patients and found decreased levels of eight proteins compared to controls, potentially indicating abnormal activity of complement system in AD.

By integrating new proteomics markers with absolute levels of Aβ42, total tau (t-tau) and p-tau in CSF, we improved the prediction accuracy from 83% to 92% of early diagnosis of AD. We found increased levels of chitinase-3-like protein 1 (CH3L1) and decreased levels of neurosecretory protein VGF (VGF) in AD compared to controls.

By exploring the CSF proteome of neuropathic pain patients before and after successful spinal cord stimulation (SCS) treatment, we found altered levels of twelve proteins, involved in neuroprotection, synaptic plasticity, nociceptive signaling and immune regulation.

To detect biomarkers for diagnosing a chronic pain state known as fibromyalgia (FM), we analyzed the CSF of FM patients using MS. We found altered levels of four proteins, representing novel biomarkers for diagnosing FM. These proteins are involved in inflammatory mechanisms, energy metabolism and neuropeptide signaling.

Finally, to facilitate fast and robust large-scale omics data handling, we developed an e-infrastructure. We demonstrated that the e-infrastructure provides high scalability, flexibility and it can be applied in virtually any fields including proteomics. This thesis demonstrates that proteomics is a promising approach for gaining deeper insight into mechanisms of nervous system disorders and find biomarkers for diagnosis of such diseases.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 82 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1385
Keyword
Bioinformatics, microservices, biomarkers, Alzheimer's disease, chronic pain, fibromyalgia, neuropathic pain, spinal cord stimulation, cloud computing, proteomics, metabolomics, software, workflows, data analysis, mass spectrometry
National Category
Geriatrics Neurology Neurosciences
Research subject
Bioinformatics; Neurology; Geriatrics
Identifiers
urn:nbn:se:uu:diva-331748 (URN)978-91-513-0111-2 (ISBN)
Public defence
2017-12-05, Rosénsalen, Akademiska sjukhuset, Ing 95/96, nbv, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2017-11-14 Created: 2017-10-17 Last updated: 2017-11-14

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