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

ABSTRACT: 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.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.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?

SUBMITTER: Swanson CR

PROVIDER: S-EPMC4609229 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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

Swanson Christine R CR Berlyand Yosef Y Xie Sharon X SX Alcalay Roy N RN Chahine Lama M LM Chen-Plotkin Alice S AS

Movement disorders : official journal of the Movement Disorder Society 20150724 12

<h4>Background</h4>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.<h4>Methods</h4>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 Par ...[more]

PMID: 26207725

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Project description:BackgroundCardiovascular disease is a leading cause of mortality in patients with juvenile-onset systemic lupus erythematosus (JSLE). Traditional factors for cardiovascular risk (CVR) prediction are less robust in younger patients. More reliable CVR biomarkers are needed for JSLE patient stratification and to identify therapeutic approaches to reduce cardiovascular morbidity and mortality in JSLE.MethodsSerum metabolomic analysis (including >200 lipoprotein measures) was performed on a discovery (n=31, median age 19) and validation (n=31, median age 19) cohort of JSLE patients. Data was analysed using cluster, receiver operating characteristic analysis and logistic regression. RNA-sequencing assessed gene expression in matched patient samples.FindingsHierarchical clustering of lipoprotein measures identified and validated two unique JSLE groups. Group-1 had an atherogenic and Group-2 had an atheroprotective lipoprotien profile. Apolipoprotein(Apo)B:ApoA1 distinguished the two groups with high specificity (96.2%) and sensitivity (96.7%). JSLE patients with high ApoB:ApoA1 ratio had increased CD8+ T-cell frequencies and a CD8+ T-cell transcriptomic profile enriched in genes associated with atherogenic processes including interferon signaling. These metabolic and immune signatures overlapped statistically significantly with lipid biomarkers associated with sub-clinical atherosclerosis in adult SLE patients and with genes overexpressed in T-cells from human atherosclerotic plaque respectively. Finally, baseline ApoB:ApoA1 ratio correlated positively with SLE disease activity index (r=0.43, p=0.0009) and negatively with Lupus Low Disease Activity State (r=-0.43, p=0.0009) over 5-year follow-up.InterpretationMulti-omic analysis identified high ApoB:ApoA1 as a potential biomarker of increased cardiometabolic risk and worse clinical outcomes in JSLE. ApoB:ApoA1 could help identify patients that require increased disease monitoring, lipid modification or lifestyle changes.FundingLupus UK, The Rosetrees Trust, British Heart Foundation, UCL & Birkbeck MRC Doctoral Training Programme and Versus Arthritis.

Dataset Information

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

Publications

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

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