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

Sjödin, Simon; Hansson, Oskar LU ; Öhrfelt, Annika; Brinkmalm, Gunnar; Zetterberg, Henrik LU ; Brinkmalm, Ann and Blennow, Kaj LU (2017) In Proteomics - Clinical Applications 11(11-12).
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:... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
alzheimer's disease, biomarker, parkinson's disease, progressive supranuclear palsy, ubiquitin
in
Proteomics - Clinical Applications
volume
11
issue
11-12
publisher
John Wiley & Sons
external identifiers
  • scopus:85038386293
  • wos:000418253600015
ISSN
1862-8346
DOI
10.1002/prca.201700100
language
English
LU publication?
yes
id
8bc5e65e-4b1b-4dba-bf09-bda69151ffc8
date added to LUP
2018-01-03 14:38:42
date last changed
2018-04-05 03:00:08
@article{8bc5e65e-4b1b-4dba-bf09-bda69151ffc8,
  abstract     = {<p>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 &lt; 0.001; Study 2, p &lt; 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.</p>},
  articleno    = {1700100},
  author       = {Sjödin, Simon and Hansson, Oskar and Öhrfelt, Annika and Brinkmalm, Gunnar and Zetterberg, Henrik and Brinkmalm, Ann and Blennow, Kaj},
  issn         = {1862-8346},
  keyword      = {alzheimer's disease,biomarker,parkinson's disease,progressive supranuclear palsy,ubiquitin},
  language     = {eng},
  month        = {12},
  number       = {11-12},
  publisher    = {John Wiley & Sons},
  series       = {Proteomics - Clinical Applications},
  title        = {Mass Spectrometric Analysis of Cerebrospinal Fluid Ubiquitin in Alzheimer's Disease and Parkinsonian Disorders},
  url          = {http://dx.doi.org/10.1002/prca.201700100},
  volume       = {11},
  year         = {2017},
}