Plasma apolipoprotein A1 associates with age at onset and motor severity in early Parkinson's disease patients - PubMed (original) (raw)

Meta-Analysis

. 2015 Oct;30(12):1648-56.

doi: 10.1002/mds.26290. Epub 2015 Jul 24.

Affiliations

Meta-Analysis

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

Christine R Swanson et al. Mov Disord. 2015 Oct.

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.

© 2015 International Parkinson and Movement Disorder Society.

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Figures

Figure 1

Figure 1. Pre-analytical variability in PPMI plasma ApoA1

Across clinical sites, site 327 (arrow) had higher-than-expected ApoA1 variability compared to other sites and to values expected based on prior ApoA1 measures at our site (A, B). Across time periods of plasma collection, the earliest period (arrow) showed higher-than-expected ApoA1 variability in neurologically normal controls only (C, D). Mean +/- SEM are indicated for each clinical site, time period, and biorepository.

Figure 2

Figure 2. Plasma ApoA1 and HDL increase over time

Plasma HDL levels correlate with ApoA1 values (A; R2 = 0.80). While no baseline differences were observed in plasma ApoA1 (B) or HDL (C) between neurologically normal controls (NC) and Parkinson disease (PD) patients, a trend towards less increase in ApoA1 levels over time was observed in PD patients (p=0.065).

Figure 3

Figure 3. Meta-analysis of >1000 PD patients confirms association of plasma ApoA1 with age at PD onset and motor severity

Plasma ApoA1 significantly associates with age at onset and motor severity (UPDRS III motor score) in a meta-analysis of five cohorts of >1000 PD patients, using linear models adjusted for age at plasma sampling and sex (A). Cox proportional hazard (CPH) models confirm the association of low plasma ApoA1 levels (red) with earlier age at onset (B) and worse (higher) UPDRS-III score (C), compared with medium (yellow) or high (green) levels of plasma ApoA1. Hazard ratio is always expressed in terms of the protective effect of increased ApoA1 expression for one tertile compared to the next. UPDRS=Unified Parkinson's disease Rating Scale.

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