Longitudinal analyses of cerebrospinal fluid α-Synuclein in prodromal and early Parkinson's disease.


Journal

Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688

Informations de publication

Date de publication:
09 2019
Historique:
received: 02 04 2019
revised: 17 06 2019
accepted: 08 07 2019
pubmed: 31 7 2019
medline: 27 6 2020
entrez: 31 7 2019
Statut: ppublish

Résumé

Aggregation of α-synuclein is central to the pathophysiology of PD. Biomarkers related to α-synuclein may be informative for PD diagnosis/progression. To analyze α-synuclein in CSF in drug-naïve PD, healthy controls, and prodromal PD in the Parkinson's Progression Markers Initiative. Over up to 36-month follow-up, CSF total α-synuclein and its association with MDS-UPDRS motor scores, cognitive assessments, and dopamine transporter imaging were assessed. The inception cohort included PD (n = 376; age [mean {standard deviation} years]: 61.7 [9.62]), healthy controls (n = 173; age, 60.9 [11.3]), hyposmics (n = 16; age, 68.3 [6.15]), and idiopathic rapid eye movement sleep behavior disorder (n = 32; age, 69.3 [4.83]). Baseline CSF α-synuclein was lower in manifest and prodromal PD versus healthy controls. Longitudinal α-synuclein decreased significantly in PD at 24 and 36 months, did not change in prodromal PD over 12 months, and trended toward an increase in healthy controls. The decrease in PD was not shown when CSF samples with high hemoglobin concentration were removed from the analysis. CSF α-synuclein changes did not correlate with longitudinal MDS-UPDRS motor scores or dopamine transporter scan. CSF α-synuclein decreases early in the disease, preceding motor PD. CSF α-synuclein does not correlate with progression and therefore does not reflect ongoing dopaminergic neurodegeneration. Decreased CSF α-synuclein may be an indirect index of changes in the balance between α-synuclein secretion, solubility, or aggregation in the brain, reflecting its overall turnover. Additional biomarkers more directly related to α-synuclein pathophysiology and disease progression and other markers to be identified by, for example, proteomics and metabolomics are needed. © 2019 International Parkinson and Movement Disorder Society.

Sections du résumé

BACKGROUND
Aggregation of α-synuclein is central to the pathophysiology of PD. Biomarkers related to α-synuclein may be informative for PD diagnosis/progression.
OBJECTIVES
To analyze α-synuclein in CSF in drug-naïve PD, healthy controls, and prodromal PD in the Parkinson's Progression Markers Initiative.
METHODS
Over up to 36-month follow-up, CSF total α-synuclein and its association with MDS-UPDRS motor scores, cognitive assessments, and dopamine transporter imaging were assessed.
RESULTS
The inception cohort included PD (n = 376; age [mean {standard deviation} years]: 61.7 [9.62]), healthy controls (n = 173; age, 60.9 [11.3]), hyposmics (n = 16; age, 68.3 [6.15]), and idiopathic rapid eye movement sleep behavior disorder (n = 32; age, 69.3 [4.83]). Baseline CSF α-synuclein was lower in manifest and prodromal PD versus healthy controls. Longitudinal α-synuclein decreased significantly in PD at 24 and 36 months, did not change in prodromal PD over 12 months, and trended toward an increase in healthy controls. The decrease in PD was not shown when CSF samples with high hemoglobin concentration were removed from the analysis. CSF α-synuclein changes did not correlate with longitudinal MDS-UPDRS motor scores or dopamine transporter scan.
CONCLUSIONS
CSF α-synuclein decreases early in the disease, preceding motor PD. CSF α-synuclein does not correlate with progression and therefore does not reflect ongoing dopaminergic neurodegeneration. Decreased CSF α-synuclein may be an indirect index of changes in the balance between α-synuclein secretion, solubility, or aggregation in the brain, reflecting its overall turnover. Additional biomarkers more directly related to α-synuclein pathophysiology and disease progression and other markers to be identified by, for example, proteomics and metabolomics are needed. © 2019 International Parkinson and Movement Disorder Society.

Identifiants

pubmed: 31361367
doi: 10.1002/mds.27806
pmc: PMC7098385
mid: NIHMS1567236
doi:

Substances chimiques

Biomarkers 0
SNCA protein, human 0
alpha-Synuclein 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1354-1364

Subventions

Organisme : NIA NIH HHS
ID : U19 AG062418
Pays : United States

Informations de copyright

© 2019 International Parkinson and Movement Disorder Society.

Références

Mov Disord. 2016 Jun;31(6):898-905
pubmed: 26878815
Mov Disord. 2016 Jan;31(1):79-85
pubmed: 26268663
Mol Neurobiol. 2019 May;56(5):3476-3483
pubmed: 30136097
Biochem Biophys Res Commun. 2006 Oct 13;349(1):162-6
pubmed: 16930553
Parkinsonism Relat Disord. 2018 Apr;49:4-8
pubmed: 29409704
Mov Disord. 2016 Oct;31(10):1535-1542
pubmed: 27548849
Parkinsonism Relat Disord. 2016 Jun;27:102-6
pubmed: 27010070
JAMA Neurol. 2017 Feb 1;74(2):163-172
pubmed: 27918765
Neurology. 2014 Jul 29;83(5):406-12
pubmed: 24975862
J Neurochem. 2019 Apr;149(1):126-138
pubmed: 30125936
Mov Disord. 2010 Nov 15;25(15):2649-53
pubmed: 21069833
Mol Neurodegener. 2018 Feb 22;13(1):9
pubmed: 29467003
Am J Pathol. 2014 Apr;184(4):966-975
pubmed: 24625392
Lancet Neurol. 2011 Mar;10(3):230-40
pubmed: 21317042
JAMA Neurol. 2017 Aug 1;74(8):933-940
pubmed: 28595287
Brain. 2010 Mar;133(Pt 3):713-26
pubmed: 20157014
JAMA Neurol. 2013 Oct;70(10):1277-87
pubmed: 23979011
Biomark Med. 2016;10(1):35-49
pubmed: 26643452
Neurology. 2017 Nov 7;89(19):1959-1969
pubmed: 29030452
Neurology. 2007 Nov 6;69(19):1843-9
pubmed: 17984452
Mov Disord. 2008 Nov 15;23(15):2129-70
pubmed: 19025984
Neurology. 2010 Sep 21;75(12):1055-61
pubmed: 20720189
Ann Clin Transl Neurol. 2016 Aug 28;3(10):812-818
pubmed: 27752516
Alzheimers Dement. 2018 Jul;14(7):869-879
pubmed: 29580670
PLoS One. 2017 May 17;12(5):e0175674
pubmed: 28520803
BMC Neurol. 2017 Nov 15;17(1):198
pubmed: 29141588
Mol Ther. 2013 Jan;21(1):31-41
pubmed: 22508489
J Neurochem. 2019 Sep;150(5):577-590
pubmed: 31069800
Mov Disord. 2007 Dec;22(16):2386-93
pubmed: 17894337
Sleep Med. 2013 Aug;14(8):744-8
pubmed: 23347909
Clin Biochem. 2000 Jul;33(5):369-75
pubmed: 11018688
Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10907-12
pubmed: 18669654
Sleep. 2012 Jun 01;35(6):835-47
pubmed: 22654203
Prog Neurobiol. 2011 Dec;95(4):629-35
pubmed: 21930184
Neurosci Lett. 2018 Oct 15;685:35-41
pubmed: 30036569
Neurology. 2016 Jul 12;87(2):168-77
pubmed: 27164658
J Neurosci. 2017 Oct 11;37(41):9799-9807
pubmed: 29021297
Mov Disord. 2017 Oct;32(10):1389-1400
pubmed: 28880418
J Neurol. 2015 Feb;262(2):294-306
pubmed: 25380583
Acta Neuropathol Commun. 2018 Feb 9;6(1):7
pubmed: 29422107

Auteurs

Brit Mollenhauer (B)

Department of Neurology, University Medical Center Goettingen, Göttingen, Germany; and Paracelsus-Elena Klinik, Kassel, Germany.

Chelsea J Caspell-Garcia (CJ)

Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA.

Christopher S Coffey (CS)

Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA.

Peggy Taylor (P)

BioLegend Inc., San Diego, California, USA.

Andy Singleton (A)

Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.

Leslie M Shaw (LM)

Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

John Q Trojanowski (JQ)

Center for Neurodegenerative Disease Research, Institute on Aging, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Morris K. Udall Center of Excellence for Parkinson's Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Mark Frasier (M)

The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.

Tanya Simuni (T)

Parkinson's Disease and Movement Disorders Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Alex Iranzo (A)

Neurological Service, Hospital Clinic de Barcelona, Barcelona, Spain.

Wolfgang Oertel (W)

Department of Neurology, Philipps University Marburg, Marburg, Germany.

Andrew Siderowf (A)

Morris K. Udall Center of Excellence for Parkinson's Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Neurology Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Daniel Weintraub (D)

Department of Neurology Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

John Seibyl (J)

Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA.

Arthur W Toga (AW)

University of Southern California, Laboratory of Neuro Imaging, Los Angeles, California, USA.

Caroline M Tanner (CM)

Department of Neurology, University of California San Francisco, San Francisco, California, USA.

Karl Kieburtz (K)

Clinical Trials Coordination Center, University of Rochester Medical Center, Rochester, New York, USA.

Lana M Chahine (LM)

Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Kenneth Marek (K)

Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA.

Douglas Galasko (D)

Department of Neurosciences, University of California, San Diego, San Diego, California, USA.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH