Biomarker Assessment in Parkinson's Disease Dementia and Dementia with Lewy Bodies by the Immunomagnetic Reduction Assay and Clinical Measures

Background: Plasma biomarker assays provide an opportunity to reassess whether Alzheimer's disease, Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB) plasma biomarkers are diagnostically useful.

Objective: We hypothesized that immunomagnetic reduction (IMR) of plasma biomarkers could differentiate between patients with PDD and DLB and healthy patients when combined with established clinical testing measures.

Methods: Plasma samples from 61 participants (12 PDD, 12 DLB, 37 controls) were analyzed using IMR to quantify amyloid-β 42 (Aβ₄₂), total tau (t-tau), phosphorylated tau at threonine 181 (p-tau181), and α-synuclein (α-syn). Receiver operating characteristic curve (ROC) analysis was used to obtain sensitivity, specificity, and area under the ROC curve. Biomarker results were combined with clinical measures from the Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment, and Hoehn-Yahr stage to optimize diagnostic test performance.

Results: Participants with PDD had higher α-syn than those with DLB and healthy participants and were distinguishable by their biomarker products Aβ₄₂×p-tau181 and Aβ₄₂×α-syn. Patients with DLB had higher p-tau181 than those with PDD and healthy participants and were distinguishable by their concentrations of α-syn×p-tau181. Plasma α-syn plus UPDRS versus either test alone increased sensitivity, specificity, and AUC when healthy patients were compared with those with PDD and DLB. Combined clinical examination scores and plasma biomarker products demonstrated utility in differentiating PDD from DLB when p-tau181 was combined with UPDRS, α-syn was combined with UPDRS, and α-syn×p-tau181 was combined with UPDRS.

Conclusions: In this pilot study, IMR plasma p-tau181 and α-syn may discriminate between PDD and DLB when used in conjunction with clinical testing.