Assessment of Plasma Biomarkers by ImmunoMagnetic Reduction in Parkinson’s Disease Dementia and Dementia with Lewy Bodies (P10-6.008)

Abstract

<h3>Objective:</h3> To use ImmunoMagnetic Reduction (IMR) assay to assess the diagnostic utility of plasma Aβ42, total Tau (t-Tau), phosphorylated Tau-181 (p-Tau-181) and α-synuclein in identifying and differentiating cases of Parkinson’s Disease Dementia (PDD) and Dementia with Lewy Bodies (DLB). <h3>Background:</h3> PDD and DLB represent pathological subtypes along a continuum of synucleinopathies. Clinical differentiation is ultimately based on arbitrary and subjectively-reported timing of cognitive and motor symptoms. Ancillary tests are invasive, costly, and exhibit suboptimal sensitivity and specificity. Developments in plasma biomarker assays have increased detection thresholds and provide the opportunity to reassess whether core PDD/DLB plasma biomarkers would be useful for diagnosis. <h3>Design/Methods:</h3> Plasma samples from 61 total subjects (37 normal controls (NC), 12 with PDD, 12 with DLB) and were sent for IMR assay to quantify α-synuclein, Aβ42, t-Tau, and p-Tau-181. To determine discrimination between NC, PDD, and DLB, receiver operating characteristic (ROC) curve analysis was used to obtain sensitivity, specificity, and area under curve (AUC). <h3>Results:</h3> Plasma p-tau levels were significantly higher in DLB compared to NC and PD (p&lt;0.05). Plasma α-synuclein levels were significantly higher in PDD compared to DLB and NC. Plasma t-Tau and Aβ42 levels did not differ between NC, PDD and DLB subjects. When plasma biomarkers were combined, Aβ42 x t-Tau revealed no differences between DLB, PDD and NC. For the α-synuclein x p-Tau-181 combination, both PDD and DLB were greater than NC. <h3>Conclusions:</h3> Investigations into the discrimination of DLB vs. PDD are rare. In this pilot study, we show that IMR assays of plasma for α-synuclein, p-Tau-181, and Aβ42 x t-tau are useful in differentiating PDD from DLB, as well as NC. Thus, our data suggest clinical utility of these novel biomarker modalities and panels. Differentiating DLB from PDD could be consequential in clinical characterization. Future studies will aim to replicate our findings on larger group sizes. <b>Disclosure:</b> Dr. Malaty has nothing to disclose. Dr. Lue has nothing to disclose. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal Pharmaceuticals. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurocrine Biosciences. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbive. Dr. Decourt has received personal compensation for serving as an employee of Cleveland Clinic. Dr. Decourt has received personal compensation in the range of $0-$499 for serving as a Reviewer with NIH. Dr. Sabbagh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai. Dr. Sabbagh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genetech=Roche. Dr. Sabbagh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novo Nordisk. Dr. Sabbagh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Dr. Sabbagh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Synaptogenix. Dr. Sabbagh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Signant Health. Dr. Sabbagh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for T3D. Dr. Sabbagh has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for EIP Pharma. Dr. Sabbagh has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Quince-Cortexyme. Dr. Sabbagh has stock in Neurotau. Dr. Sabbagh has stock in Seq Biomarque. Dr. Sabbagh has stock in uMethod Health. Dr. Sabbagh has stock in Athira. Dr. Sabbagh has stock in Lighthouse Pharmaceuticals. Dr. Sabbagh has stock in Alzheom. The institution of Dr. Sabbagh has received research support from NIH. The institution of Dr. Sabbagh has received research support from ADDF. Dr. Sabbagh has received publishing royalties from a publication relating to health care.