Cerebrospinal fluid biomarkers for Parkinson's disease

a systematic review

Bidragets oversatte titel: Biomarkører i spinalvæsken ved Parkinson's sygdom - et systematisk review.

Andreas Dammann Andersen, Michael Binzer, Egon Stenager, Jan Bert Gramsbergen

Publikation: Bidrag til tidsskriftReviewForskningpeer review

Resumé

Diagnosticering af Parkinson's sygdom (PD) er baseret på den kliniske udvikling af sygdommen samt en fysisk undersøgelse af patienten, men fejldiagnosticering sker hyppigt; specielt i tidlige stadier. Biomarkører for PD kan muliggøre en tidligere og mere præcis diagnosticering samt monitorering af den medicinske behandling af patienterne med både dopamin-erstattende midler og sygdomsmodulerende behandlinger. På grund af udviklingen inden for analytisk kemi, kan man nu detektere et stort antal molekyler i plasma og spinalvæsken, som kan være associeret med patofysiologien eller patogenesen ved PD.
Dette systematiske review inkluderer studier i biomarkører i spinalvæsken, som fokuserer på forskellige sygdomsmekanismer: Oxidativt stress, neuroinflammation, lysosomal dysfunktion og proteiner involveret i PD og andre neurodegenerative lidelser. Der fokuseres på fire kliniske domæner: Biomarkørernes evne til (1) at adskille individer med PD fra raske individer samt individer med andre neurodegenerative lidelser, såvel som biomarkørernes relation til (2) sygdomsvarighed efter diagnosticering, (3) sygdommens sværhedsgrad (motor-symptomer) og (4) kognitiv dysfunktion.
Oligomer alpha-synuclein kan spille en rolle i at skelne mellem PD og kontroller. Via metabolomics har man identificeret forandringer i purin- og tryptofan-metabolismen hos PD-patienter. Neurofilament light chain (NfL) spiller en signifikant rolle med hensyn til at adskille PD fra andre neurodegenerative lidelser. Flere markører for oxidativt stress er relateret til sygdommens sværhedsgrad. Antioxidanten urat har derudover en prognostisk værdi i forhold til sygdommens sværhedsgrad. Forhøjede niveauer af amyloid- og tau-proteiner korrelerer med kognitiv svækkelse og har måske en prognostisk værdi i forhold til kognitiv svækkelse ved PD.
Fremtidig forskning i form af større longitudinelle studier, som kan bekræfte forudgående studiers fund med hensyn til mulige biomarkør-kandidater, vil formentlig være en god fremgangsmåde, ligesom brugen af metabolomics, som kan identificere et stort antal potentielle biomarkører.
OriginalsprogEngelsk
TidsskriftActa Neurologica Scandinavica
Vol/bind135
Udgave nummer1
Sider (fra-til)34-56
ISSN0001-6314
DOI
StatusUdgivet - 2017

Fingeraftryk

Parkinson Disease
Cerebrospinal Fluid
Neurodegenerative Diseases
Intermediate Filaments
Uric Acid
Diagnostic Errors
Tryptophan
Physical Examination
Longitudinal Studies
Research

Emneord

  • Parkinson's sygdom
  • Biomarkør
  • Spinalvæske
  • Systematisk review
  • alpha-Synuclein
  • Metabolomics
  • Amyloid beta
  • tau protein
  • neurofilament light chain

Citer dette

@article{e19e54b001ed4b5ab879c6dd90ffc138,
title = "Cerebrospinal fluid biomarkers for Parkinson's disease: a systematic review",
abstract = "Diagnosis of Parkinson's disease (PD) relies on clinical history and physical examination, but misdiagnosis is common in early stages. Identification of biomarkers for PD may allow early and more precise diagnosis and monitoring of dopamine replacement strategies and disease modifying treatments. Developments in analytical chemistry allow the detection of large numbers of molecules in plasma or cerebrospinal fluid, associated with the pathophysiology or pathogenesis of PD. This systematic review includes cerebrospinal fluid biomarker studies focusing on different disease pathways: oxidative stress, neuroinflammation, lysosomal dysfunction and proteins involved in PD and other neurodegenerative disorders, focusing on four clinical domains: their ability to (1) distinguish PD from healthy subjects and other neurodegenerative disorders as well as their relation to (2) disease duration after initial diagnosis, (3) severity of disease (motor symptoms) and (4) cognitive dysfunction. Oligomeric alpha‐synuclein might be helpful in the separation of PD from controls. Through metabolomics, changes in purine and tryptophan metabolism have been discovered in patients with PD. Neurofilament light chain (NfL) has a significant role in distinguishing PD from other neurodegenerative diseases. Several oxidative stress markers are related to disease severity, with the antioxidant urate also having a prognostic value in terms of disease severity. Increased levels of amyloid and tau‐proteins correlate with cognitive decline and may have prognostic value for cognitive deficits in PD. In the future, larger longitudinal studies, corroborating previous research on viable biomarker candidates or using metabolomics identifying a vast amount of potential biomarkers, could be a good approach.",
keywords = "Parkinson's sygdom, Biomark{\o}r, Spinalv{\ae}ske, Systematisk review, alpha-Synuclein, Metabolomics, Amyloid beta, tau protein, neurofilament light chain",
author = "{Dammann Andersen}, Andreas and Michael Binzer and Egon Stenager and Gramsbergen, {Jan Bert}",
note = "{\circledC} 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",
year = "2017",
doi = "10.1111/ane.12590",
language = "English",
volume = "135",
pages = "34--56",
journal = "Acta Neurologica Scandinavica",
issn = "0001-6314",
publisher = "Wiley-Blackwell Munksgaard",
number = "1",

}

Cerebrospinal fluid biomarkers for Parkinson's disease : a systematic review. / Dammann Andersen, Andreas; Binzer, Michael; Stenager, Egon; Gramsbergen, Jan Bert.

I: Acta Neurologica Scandinavica, Bind 135, Nr. 1, 2017, s. 34-56.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

TY - JOUR

T1 - Cerebrospinal fluid biomarkers for Parkinson's disease

T2 - a systematic review

AU - Dammann Andersen, Andreas

AU - Binzer, Michael

AU - Stenager, Egon

AU - Gramsbergen, Jan Bert

N1 - © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2017

Y1 - 2017

N2 - Diagnosis of Parkinson's disease (PD) relies on clinical history and physical examination, but misdiagnosis is common in early stages. Identification of biomarkers for PD may allow early and more precise diagnosis and monitoring of dopamine replacement strategies and disease modifying treatments. Developments in analytical chemistry allow the detection of large numbers of molecules in plasma or cerebrospinal fluid, associated with the pathophysiology or pathogenesis of PD. This systematic review includes cerebrospinal fluid biomarker studies focusing on different disease pathways: oxidative stress, neuroinflammation, lysosomal dysfunction and proteins involved in PD and other neurodegenerative disorders, focusing on four clinical domains: their ability to (1) distinguish PD from healthy subjects and other neurodegenerative disorders as well as their relation to (2) disease duration after initial diagnosis, (3) severity of disease (motor symptoms) and (4) cognitive dysfunction. Oligomeric alpha‐synuclein might be helpful in the separation of PD from controls. Through metabolomics, changes in purine and tryptophan metabolism have been discovered in patients with PD. Neurofilament light chain (NfL) has a significant role in distinguishing PD from other neurodegenerative diseases. Several oxidative stress markers are related to disease severity, with the antioxidant urate also having a prognostic value in terms of disease severity. Increased levels of amyloid and tau‐proteins correlate with cognitive decline and may have prognostic value for cognitive deficits in PD. In the future, larger longitudinal studies, corroborating previous research on viable biomarker candidates or using metabolomics identifying a vast amount of potential biomarkers, could be a good approach.

AB - Diagnosis of Parkinson's disease (PD) relies on clinical history and physical examination, but misdiagnosis is common in early stages. Identification of biomarkers for PD may allow early and more precise diagnosis and monitoring of dopamine replacement strategies and disease modifying treatments. Developments in analytical chemistry allow the detection of large numbers of molecules in plasma or cerebrospinal fluid, associated with the pathophysiology or pathogenesis of PD. This systematic review includes cerebrospinal fluid biomarker studies focusing on different disease pathways: oxidative stress, neuroinflammation, lysosomal dysfunction and proteins involved in PD and other neurodegenerative disorders, focusing on four clinical domains: their ability to (1) distinguish PD from healthy subjects and other neurodegenerative disorders as well as their relation to (2) disease duration after initial diagnosis, (3) severity of disease (motor symptoms) and (4) cognitive dysfunction. Oligomeric alpha‐synuclein might be helpful in the separation of PD from controls. Through metabolomics, changes in purine and tryptophan metabolism have been discovered in patients with PD. Neurofilament light chain (NfL) has a significant role in distinguishing PD from other neurodegenerative diseases. Several oxidative stress markers are related to disease severity, with the antioxidant urate also having a prognostic value in terms of disease severity. Increased levels of amyloid and tau‐proteins correlate with cognitive decline and may have prognostic value for cognitive deficits in PD. In the future, larger longitudinal studies, corroborating previous research on viable biomarker candidates or using metabolomics identifying a vast amount of potential biomarkers, could be a good approach.

KW - Parkinson's sygdom

KW - Biomarkør

KW - Spinalvæske

KW - Systematisk review

KW - alpha-Synuclein

KW - Metabolomics

KW - Amyloid beta

KW - tau protein

KW - neurofilament light chain

U2 - 10.1111/ane.12590

DO - 10.1111/ane.12590

M3 - Review

VL - 135

SP - 34

EP - 56

JO - Acta Neurologica Scandinavica

JF - Acta Neurologica Scandinavica

SN - 0001-6314

IS - 1

ER -