TY - JOUR
T1 - Fluid biomarkers in multiple system atrophy
T2 - A review of the MSA Biomarker Initiative
AU - Laurens, Brice
AU - Constantinescu, Radu
AU - Freeman, Roy
AU - Gerhard, Alexander
AU - Jellinger, Kurt
AU - Jeromin, Andreas
AU - Krismer, Florian
AU - Mollenhauer, Brit
AU - Schlossmacher, Michael G
AU - Shaw, Leslie M
AU - Verbeek, Marcel M
AU - Wenning, Gregor K
AU - Winge, Kristian
AU - Zhang, Jing
AU - Meissner, Wassilios G
N1 - Copyright © 2015 Elsevier Inc. All rights reserved.
PY - 2015/8
Y1 - 2015/8
N2 - Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target engagement for future clinical trials. We here review candidate fluid biomarkers for MSA and provide considerations for further developments and harmonization of standard operating procedures. A PubMed search was performed until April 24, 2015 to review the literature with regard to candidate blood and cerebrospinal fluid (CSF) biomarkers for MSA. Abstracts of 1760 studies were retrieved and screened for eligibility. The final list included 60 studies assessing fluid biomarkers in patients with MSA. Most studies have focused on alpha-synuclein, markers of axonal degeneration or catecholamines. Their results suggest that combining several CSF fluid biomarkers may be more successful than using single markers, at least for the diagnosis. Currently, the clinically most useful markers may comprise a combination of the light chain of neurofilament (which is consistently elevated in MSA compared to controls and Parkinson's disease), metabolites of the catecholamine pathway and proteins such as α-synuclein, DJ-1 and total-tau. Beyond future efforts in biomarker discovery, the harmonization of standard operating procedures will be crucial for future success.
AB - Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target engagement for future clinical trials. We here review candidate fluid biomarkers for MSA and provide considerations for further developments and harmonization of standard operating procedures. A PubMed search was performed until April 24, 2015 to review the literature with regard to candidate blood and cerebrospinal fluid (CSF) biomarkers for MSA. Abstracts of 1760 studies were retrieved and screened for eligibility. The final list included 60 studies assessing fluid biomarkers in patients with MSA. Most studies have focused on alpha-synuclein, markers of axonal degeneration or catecholamines. Their results suggest that combining several CSF fluid biomarkers may be more successful than using single markers, at least for the diagnosis. Currently, the clinically most useful markers may comprise a combination of the light chain of neurofilament (which is consistently elevated in MSA compared to controls and Parkinson's disease), metabolites of the catecholamine pathway and proteins such as α-synuclein, DJ-1 and total-tau. Beyond future efforts in biomarker discovery, the harmonization of standard operating procedures will be crucial for future success.
U2 - 10.1016/j.nbd.2015.05.004
DO - 10.1016/j.nbd.2015.05.004
M3 - Journal article
C2 - 25982836
VL - 80
SP - 29
EP - 41
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
ER -