Plasma apolipoprotein A1 as a biomarker for Parkinson disease

Abstract

Objective To identify plasma-based biomarkers for Parkinson's 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 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 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.

Glucocerebrosidase mutations and the pathogenesis of Parkinson disease

“…Low levels of plasma ApoA1 have also been proposed as a significant risk factor for PD, and the concentrations also correlate with putaminal loss on Dopamine Transporter (DaT) scans (Qiang et al, 2013). Lower ApoA1 levels are associated with more severe DaT deficit, even after adjusting for age and gender.…”

Biomarker sources for Parkinson's disease: Time to shed tears?

“…A significant association could be detected between apolipoprotein A1 (ApoA1) and the age of onset of PD: The risk for developing PD decreased by 26% for each increasing tertile of ApoA1 expression [19]. This result could be confirmed in an independent follow-up study [19]. ApoA1 was found to be a significant predictor of the United Parkinson's Disease Rating Scale part III score.…”

“…However, since more than 95% of the a-syn and DJ-1 in serum/plasma are derived from red blood cells, even the correction for this potential source of noise was not able to improve any brainspecific signal [18]. A significant association could be detected between apolipoprotein A1 (ApoA1) and the age of onset of PD: The risk for developing PD decreased by 26% for each increasing tertile of ApoA1 expression [19]. This result could be confirmed in an independent follow-up study [19].…”

“…ApoA1 was found to be a significant predictor of the United Parkinson's Disease Rating Scale part III score. When correlated with the putaminal dopamine transporter (DAT)-mediated uptake of [123I]-b-CIT a lower ApoA1 level was associated with a more severe deficit [19].…”

Identification of an Immune-Neuroendocrine Biomarker Panel for Detection of Depression: A Joint Effects Statistical Approach

“…The 243 analyte DiscoveryMAP platform is a more recent upgraded version of the original 142 analyte multiplex platform containing around 100 additional analytes. Both multiplexes consist of immune/inflammatory, endocrine and metabolic analytes previously implicated in several neurological/psychiatric disorders such as Alzheimer's disease [34], autism [35], multiple sclerosis [36], Parkinson's disease [37], schizophrenia [38], depression [19,29] and bipolar disorder [39]. All assays were conducted in the Clinical Laboratory Improved Amendments (CLIA)-certified laboratory at Myriad-RBM (Austin, Tex., USA; see details in [40]).…”