Document Detail


Plasma apolipoprotein A1 as a biomarker for Parkinson disease.
MedLine Citation:
PMID:  23447138     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To identify plasma-based biomarkers for Parkinson disease (PD) risk.
METHODS: In a discovery cohort of 152 PD patients, plasma levels of 96 proteins were measured by multiplex immunoassay; proteins associated with age at PD onset were identified by linear regression. Findings from discovery screening were then assessed in a second cohort of 187 PD patients, using a different technique. Finally, in a third cohort of at-risk, asymptomatic individuals enrolled in the Parkinson's Associated Risk Study (PARS, n = 134), plasma levels of the top candidate biomarker were measured, and dopamine transporter (DAT) imaging was performed, to evaluate the association of plasma protein levels with dopaminergic system integrity.
RESULTS: One of the best candidate protein biomarkers to emerge from discovery screening was apolipoprotein A1 (ApoA1; p = 0.001). Low levels of ApoA1 correlated with earlier PD onset, with a 26% decrease in risk of developing PD associated with each tertile increase in ApoA1 (Cox proportional hazards, p < 0.001, hazard ratio = 0.742). The association between plasma ApoA1 levels and age at PD onset was replicated in an independent cohort of PD patients (p < 0.001). Finally, in the PARS cohort of high-risk, asymptomatic subjects, lower plasma levels of ApoA1 were associated with greater putaminal DAT deficit (p = 0.037).
INTERPRETATION: Lower ApoA1 levels correlate with dopaminergic system vulnerability in symptomatic PD patients and in asymptomatic individuals with physiological reductions in dopamine transporter density consistent with prodromal PD. Plasma ApoA1 may be a new biomarker for PD risk.
Authors:
Judy K Qiang; Yvette C Wong; Andrew Siderowf; Howard I Hurtig; Sharon X Xie; Virginia M-Y Lee; John Q Trojanowski; Dora Yearout; James B Leverenz; Thomas J Montine; Matt Stern; Susan Mendick; Danna Jennings; Cyrus Zabetian; Ken Marek; Alice S Chen-Plotkin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-08-06
Journal Detail:
Title:  Annals of neurology     Volume:  74     ISSN:  1531-8249     ISO Abbreviation:  Ann. Neurol.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-09-16     Completed Date:  2013-11-07     Revised Date:  2014-08-07    
Medline Journal Info:
Nlm Unique ID:  7707449     Medline TA:  Ann Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  119-27     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 American Neurological Association.
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MeSH Terms
Descriptor/Qualifier:
Age of Onset
Aged
Apolipoprotein A-I / blood*
Biological Markers / blood
Cohort Studies
Dopamine Plasma Membrane Transport Proteins / metabolism
Female
Humans
Male
Middle Aged
Motor Activity / physiology
Parkinson Disease / blood*,  physiopathology,  radionuclide imaging
Risk Factors
Sex Factors
Statistics as Topic
Statistics, Nonparametric
Tomography, Emission-Computed, Single-Photon
Tropanes / diagnostic use
Grant Support
ID/Acronym/Agency:
AG-033101/AG/NIA NIH HHS; K08 AG033101/AG/NIA NIH HHS; P30 AG010124/AG/NIA NIH HHS; P50 NS053488/NS/NINDS NIH HHS; P50 NS053488/NS/NINDS NIH HHS; P50 NS062684/NS/NINDS NIH HHS; P50 NS062684/NS/NINDS NIH HHS; R01 NS065070/NS/NINDS NIH HHS; R01 NS065070/NS/NINDS NIH HHS; U01 NS082134/NS/NINDS NIH HHS; U01NS082134/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoprotein A-I; 0/Biological Markers; 0/Dopamine Plasma Membrane Transport Proteins; 0/Tropanes; 155797-99-2/2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane
Comments/Corrections

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