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Plasma apolipoprotein A1 as a biomarker for Parkinson disease.
Ann Neurol. 2013 Jul; 74(1):119-27.AN

Abstract

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+Show Affiliations

Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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.

Language

eng

PubMed ID

23447138

Citation

Qiang, Judy K., et al. "Plasma Apolipoprotein A1 as a Biomarker for Parkinson Disease." Annals of Neurology, vol. 74, no. 1, 2013, pp. 119-27.
Qiang JK, Wong YC, Siderowf A, et al. Plasma apolipoprotein A1 as a biomarker for Parkinson disease. Ann Neurol. 2013;74(1):119-27.
Qiang, J. K., Wong, Y. C., Siderowf, A., Hurtig, H. I., Xie, S. X., Lee, V. M., Trojanowski, J. Q., Yearout, D., B Leverenz, J., Montine, T. J., Stern, M., Mendick, S., Jennings, D., Zabetian, C., Marek, K., & Chen-Plotkin, A. S. (2013). Plasma apolipoprotein A1 as a biomarker for Parkinson disease. Annals of Neurology, 74(1), 119-27. https://doi.org/10.1002/ana.23872
Qiang JK, et al. Plasma Apolipoprotein A1 as a Biomarker for Parkinson Disease. Ann Neurol. 2013;74(1):119-27. PubMed PMID: 23447138.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Plasma apolipoprotein A1 as a biomarker for Parkinson disease. AU - Qiang,Judy K, AU - Wong,Yvette C, AU - Siderowf,Andrew, AU - Hurtig,Howard I, AU - Xie,Sharon X, AU - Lee,Virginia M-Y, AU - Trojanowski,John Q, AU - Yearout,Dora, AU - B Leverenz,James, AU - Montine,Thomas J, AU - Stern,Matt, AU - Mendick,Susan, AU - Jennings,Danna, AU - Zabetian,Cyrus, AU - Marek,Ken, AU - Chen-Plotkin,Alice S, Y1 - 2013/08/06/ PY - 2012/08/28/received PY - 2013/02/04/revised PY - 2013/02/15/accepted PY - 2013/3/1/entrez PY - 2013/3/1/pubmed PY - 2013/11/8/medline SP - 119 EP - 27 JF - Annals of neurology JO - Ann Neurol VL - 74 IS - 1 N2 - 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. SN - 1531-8249 UR - https://www.unboundmedicine.com/medline/citation/23447138/Plasma_apolipoprotein_A1_as_a_biomarker_for_Parkinson_disease_ L2 - https://doi.org/10.1002/ana.23872 DB - PRIME DP - Unbound Medicine ER -