Objective: To evaluate the relative performance of plasma p-tau217 and p-tau181 as biomarkers of Alzheimer’s disease (AD) co-pathology across the Lewy body disorders (LBD) spectrum.
Background: Plasma phosphorylated-tau at threonine 217 (p-tau217) and threonine 181 (p-tau181) are scalable, minimally invasive biomarkers of AD pathology. Concomitant AD pathology frequently occurs in LBD and is thought to contribute to their clinical heterogeneity. However, the existing literature has predominantly focused on p-tau181, with comparatively limited investigation of p-tau217.[1–3]
Method: Plasma p-tau217 and p-tau181 were measured in 74 LBD patients (PD-NC, n=21; PD-MCI, n=33; PDD/DLB, n=19) and 83 community-based older adults (≥65 years). The protocol included brain MRI, clinical, II-level neuropsychological assessment, and blood sampling. An overview of the study design is summarized in [Figure 1].
Associations with cognitive impairment, motor severity (H&Y), functional independence (PD-CFRS) and neurostructural measures—including global atrophy,[4] hippocampal volume, and an MRI AD-signature [5]—were assessed using correlation and dominance analyses.
Results: Plasma p-tau217 emerged as a more robust indicator of AD co-pathology than p-tau181 in our LBD cohort. Elevated p-tau217 levels were associated with AD-like neurostructural changes, greater motor severity, multidomain cognitive deficits, and reduced functional independence. Similarly, in a dementia-free older adult cohort, p-tau217 showed associations with MRI AD-signature and poorer cognition—particularly global cognition and memory—while language showed comparable associations for both p-tau markers. Together, there results support p-tau217 as a sensitive marker of concomitant AD-pathology across the LBD spectrum, even in non-demented PD.
Conclusion: Plasma p-tau217 may serve as a cost-effective screening biomarker of AD co-pathology across the LBD cognitive spectrum, including non-demented Parkinson’s disease individuals.
Figure 1
References: REFERENCES
1. Ye R, Kivisäkk P, Goodheart A, et al. Plasma Phosphorylated Tau181 as a Biomarker for Alzheimer’s Disease Co-Pathology in Lewy Body Disease. Movement Disorders 2025;40(9):1930–1939. https://doi.org/10.1002/mds.30238
2. Hall S, Janelidze S, Londos E, et al. Plasma Phospho-Tau Identifies Alzheimer’s Co-Pathology in Patients with Lewy Body Disease. Movement Disorders 2021;36(3):767–771. https://doi.org/10.1002/mds.28370
3. Musso G, Fiorenzato E, Misenti V, et al. Detecting amyloid and tau pathology in Parkinson’s disease, 4R-tauopathies and control subjects with plasma pTau217. Front Neurol;16. https://doi.org/10.3389/fneur.2025.1638852
4. Orellana C, Ferreira D, Muehlboeck J-S, et al. Measuring Global Brain Atrophy with the Brain Volume/Cerebrospinal Fluid Index: Normative Values, Cut-Offs and Clinical Associations. Neurodegener Dis 2016;16(1–2):77–86. https://doi.org/10.1159/000442443
5. Shiino A, Shirakashi Y, Ishida M, Tanigaki K. Machine learning of brain structural biomarkers for Alzheimer’s disease (AD) diagnosis, prediction of disease progression, and amyloid beta deposition in the Japanese population. Alzheimers Dement (Amst) 2021;13(1):e12246. https://doi.org/10.1002/dad2.12246
To cite this abstract in AMA style:
E. Fiorenzato, S. Cauzzo, G. Musso, R. Biundo, C. Ceolin, C. Fogliano, C. Cosma, W. Meissner, V. Misenti, S. Moz, ML. Nasi, F. Vianello, R. Manara, M. Montagnana, G. Sergi, A. Antonini. Plasma p-tau217 outperforms p-tau181 as a biomarker of Alzheimer’s disease co-pathology in the Lewy Body Disorders spectrum [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/plasma-p-tau217-outperforms-p-tau181-as-a-biomarker-of-alzheimers-disease-co-pathology-in-the-lewy-body-disorders-spectrum/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/plasma-p-tau217-outperforms-p-tau181-as-a-biomarker-of-alzheimers-disease-co-pathology-in-the-lewy-body-disorders-spectrum/