期刊
MOVEMENT DISORDERS
卷 30, 期 12, 页码 1648-1656出版社
WILEY
DOI: 10.1002/mds.26290
关键词
apolipoprotein A1; biomarker; Parkinson's disease
资金
- Michael J. Fox Foundation for Parkinson's Research
- AbbVie
- Avid Radiopharmaceuticals
- Biogen Idec
- Bristol-Meyers Squibb
- Covance
- GE Healthcare
- Genentech
- GlaxoSmithKline
- Eli Lilly and Company
- Lundbeck
- Merck
- Meso Scale Discovery
- Pfizer Inc.
- Piramal Imaging
- Roche CNS group
- UCB
- National Institutes of Health (NIH) [P50 NS053488, U01 NS082134, R01 NS082265, NINDS: K02 NS080915, UL1 TR000040, UL1 RR024156]
- Doris Duke Charitable Foundation
- Burroughs Wellcome Fund
- Benaroya Fund
- Brody Family Trust Fund
- Parkinson's Disease Foundation
- Michael J. Fox Foundation
- Smart Foundation
- Sanofi/Genzyme
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-naive 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 integrityearlier age at PD onset and greater motor severityin early-stage, drug-naive 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. (c) 2015 International Parkinson and Movement Disorder Society
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