Plasma p‐tau217 Versus p‐tau181 in Parkinson’s Disease: Differential Associations with Alzheimer’s Disease‐Related Neurostructural Changes and Cognitive Function
Movement Disorders. 2026-06-15; :
DOI: 10.1002/mds.70392
Abstract
Background
Plasma phosphorylated‐tau at threonine‐217 (p‐tau217) and threonine‐181 (p‐tau181) are scalable, minimally invasive biomarkers of Alzheimer’s disease (AD) pathology. In Parkinson’s disease (PD), AD co‐pathology may contribute to its clinical heterogeneity. However, the existing literature has predominantly focused on p‐tau181, with comparatively limited investigation of p‐tau217.
Objective
The aim is to evaluate plasma p‐tau217 and p‐tau181 as biomarkers of AD co‐pathology across the PD cognitive spectrum, relative to a cohort of dementia‐free older adults.
Methods
Plasma p‐tau217 and p‐tau181 were measured in 70 PD patients and 83 older adults. Associations with cognitive impairment, disease severity (Hoehn‐and‐Yahr), and neurostructural measures—including global atrophy, hippocampal volume, and a magnetic resonance imaging‐based AD signature—were assessed using correlation and dominance analyses.
Results
Both p‐tau217 and 181 were higher in PD with cognitive impairment and dementia compared with cognitively normal PD. P‐tau217 showed stronger associations than p‐tau181 with AD‐like neurostructural changes, multidomain cognitive deficits, greater disease severity, and reduced functional independence.
Conclusions
Plasma p‐tau217 and p‐tau181 may serve as scalable markers of AD‐related processes associated with neurostructural, clinical, and cognitive outcomes in PD. © 2026 The Author(s).
Movement Disorders
published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.