Plasma pTau217 as a Biomarker for Alzheimer’s Co-Pathology in Parkinson’s Disease

Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by a complex and heterogeneous clinical presentation. Initially considered a primarily motor disorder, it is now well established that non-motor symptoms, including cognitive dysfunction and dementia, play a significant role in disease progression. Cognitive decline in PD is associated with greater functional decline, loss of independence, and higher mortality risk. Neuropathological studies revealed that PD patients with cognitive deficits often exhibit a more complex pathological profile, frequently involving Alzheimer's disease (AD) co-pathology. The advent of biomarkers has enabled the in vivo assessment of underlying pathological processes, particularly those related to AD, as well as further enhances our understanding of neurodegenerative disorders. Among the biomarker’s detection methods, blood sampling is the most scalable, rapid, and non-invasive for research and clinical use. The blood-based biomarker phosphorylated-tau 217 (p-tau217) has demonstrated high accuracy in detecting AD-related neuropathological changes and is considered an indirect measure of amyloid-beta plaques and tau tangles. Therefore, this study aims to evaluate the utility of plasma p-tau217 in detecting AD co-pathology in PD patients. Plasma p-tau217 levels were measured using the Lumipulse G1200 assay (research-use-only) in all participants. The study cohort was composed of 66 patients with Parkinson’s Disease (PD) and 71 control subjects. All participants underwent neuropsychological assessments, including the Montreal Cognitive Assessment (MoCA) and Minimental State Examination (MMSE). PD patients were classified into patients with normal cognition (PD-NC n=18), Mild Cognitive Impairment (PD-MCI n=21), and dementia, including both Parkinson’s Disease Dementia and Dementia with Lewy Body (PDD/DLB =11). PD and DLB patients, belonging to the spectrum of Lewy body disorders, were combined into the same group given the absence of significant differences in p-tau217 concentrations. Control subjects were categorized as subjects with Mild Cognitive Impairment (MCI n=26) or cognitively unimpaired (CU n= 51). Results showed that the levels of plasma p-tau217 were significantly different across the PD cognitive spectrum: PD-NC shows lower plasma p-tau217 levels than PD-MCI (W=4.12, p=0.030) and PDD/DLB (W=4.04, p=0.035). Moreover, plasma p-tau217 showed significant correlation with tests for global cognition: MoCA (r2 = –0.304, p=0.019) and MMSE (r2 = –0.287, p=0.027), outperforming the other blood biomarkers. In conclusion, the study found plasma p-tau217 concentration in PD patients with cognitive disorders, but no positive cases in PD patients without cognitive deficits, demonstrating the utility of this blood-based marker to detect AD co-pathology.