Plasma apolipoprotein A1 associates with age at onset and motor severity in early Parkinson's disease patients

Mov Disord. 2015 Oct;30(12):1648-56. doi: 10.1002/mds.26290. Epub 2015 Jul 24.

Abstract

Background: Development of robust plasma-based biomarkers in Parkinson's disease (PD) could lead to new approaches for identifying those at risk for PD and developing novel therapies. Here, we validate plasma apolipoprotein A1 (ApoA1) as a correlate of age at onset and motor severity in PD.

Methods: Plasma ApoA1 and high-density lipoprotein at baseline, 6 months, and 12 months were measured in 254 research volunteers (154 patients with PD and 100 normal controls) enrolled in the Parkinson's Progression Markers Initiative (PPMI) study.

Results: Lower baseline plasma ApoA1 levels associate with an earlier age at PD onset in early-stage, drug-naïve PPMI PD patients (P = 0.023). Moreover, lower baseline ApoA1 levels trend toward association with worse motor severity in PPMI PD patients (p = 0.080). Over 12 months of follow-up, plasma ApoA1 levels do not predict motor decline in the PPMI PD cohort. Finally, a meta-analysis of five PD cohorts encompassing >1,000 patients confirms significant association of lower plasma ApoA1 with earlier age at PD onset (P < 0.001) and greater motor severity (P < 0.001).

Conclusions: Our results confirm the previously reported association of lower plasma ApoA1 levels with two clinical features suggesting poorer dopaminergic system integrity-earlier age at PD onset and greater motor severity-in early-stage, drug-naïve PD patients. This is the first report of a plasma-based biomarker evaluated in the PPMI study. Future investigations are warranted evaluating plasma ApoA1 as a longitudinal correlate of disease progression as well as investigating the potential of ApoA1 as a therapeutic target in PD.

Keywords: Parkinson's disease; apolipoprotein A1; biomarker.

Publication types

  • Meta-Analysis
  • Multicenter Study
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Age of Onset
  • Aged
  • Apolipoprotein A-I / blood*
  • Cohort Studies
  • Female
  • Humans
  • International Cooperation
  • Lipids / blood
  • Male
  • Middle Aged
  • Motor Activity / physiology*
  • Parkinson Disease / blood*
  • Parkinson Disease / physiopathology*
  • Severity of Illness Index
  • Statistics as Topic
  • Time Factors

Substances

  • Apolipoprotein A-I
  • Lipids