Plasma p‐tau217 Versus p‐tau181 in Parkinson's Disease: Differential Associations with Alzheimer's Disease‐Related Neurostructural Changes and Cognitive Function

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.