Objective: The objectives of this study are to compare plasma phosphorylated tau-217 (P-tau217) levels in Parkinson’s disease (PD) with versus without Alzheimer’s disease (AD) copathology and evaluate its prognostic value for cognitive decline.
Background: AD pathology commonly co-occurs in the brains of people with Lewy body disorders, including PD and dementia with Lewy bodies (DLB) and associates with worse outcomes. Recently developed blood-based biomarkers can reliably detect amyloid and tau pathology in AD but have not yet been validated in PD/DLB.
Method: P-tau217 concentrations were measured antemortem in cases with a neuropathological diagnosis of Lewy Body pathology (N=46 PD, N=10 DLB) from the UPenn Center for Neurodegenerative Disease Research cohort; and in healthy participants (HC; N=64). Primary analysis evaluated group differences and the diagnostic performance of P-tau217 using AD pathology at autopsy as standard-of-truth. Furthermore, the impact of plasma P-tau217 on cognitive decline was assessed in patients with a baseline clinical diagnosis of PD (N=273) with available longitudinal assessments. In a subset of cases, serial P-tau217 concentrations were measured at baseline and at timepoints in which progression from normal cognition to mild cognitive impairment or dementia was observed. Mixed-effects linear regression and Cox regression models (age- and sex-adjusted) were used to evaluate P-tau217 concentrations as predictor of change in longitudinal Mattis Dementia Rating Scale (DRS) score and time to cognitive diagnosis conversion.
Results: P-tau217 concentrations were greater in PD compared to HC (P<0.01), and in PD/DLB pathology cases with (med 0.3 [IQR 0.2-0.4]) versus without (med 0.1 [IQR 0.1-0.2]) AD copathology (p<0.01). PD patients showing cognitive decline had greater increases in serially measured P-tau217 compared to those without cognitive decline (p=0.02). Higher P-tau217 levels associated with faster rates of decline in DRS (p=0.02) and a higher risk for cognitive diagnosis conversion (HR=1.918, p=0.01).
Conclusion: Plasma P-tau217 can detect AD copathology in PD and show potential value for predicting cognitive decline. Future studies will evaluate associations between plasma P-tau217 and imaging and clinical outcomes, in consideration for use of amyloid-targeting therapies in PD/DLB patients.
To cite this abstract in AMA style:
T. Tropea, P. Aldea Stevenson, M. Flitter, D. Meehan, A. Morris, M. Lu, L. Iaccarino, E. Collins, M. Hodsdon, L. Shaw, E. Lee, D. Weintraub, A. Chen-Plotkin, M. Mintun, A. Siderowf. Plasma P-tau217 detects Alzheimer’s co-pathology and predicts cognitive decline in Parkinson’s disease [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/plasma-p-tau217-detects-alzheimers-co-pathology-and-predicts-cognitive-decline-in-parkinsons-disease/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/plasma-p-tau217-detects-alzheimers-co-pathology-and-predicts-cognitive-decline-in-parkinsons-disease/