Plasma Phosphorylated Tau217 as a Biomarker in Dementia with Lewy Bodies: Associations with Clinical Characteristics

Dementia with Lewy Bodies (DLB) is the second most common type of neurodegenerative dementia in older adults, yet it remains vastly underdiagnosed and misclassified, due to overlapping pathology with Alzheimer’s Disease (AD). A substantial proportion of DLB cases exhibit coexisting AD pathology, including aggregates of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs), which can influence both the clinical presentation and prognosis of the disease. While methods such as Positron Emission Tomography (PET) imaging and cerebrospinal fluid (CSF) analysis are established tools for detecting amyloid pathology, a less invasive and cost-effective alternative is the emergence of plasma-based biomarkers such as phosphorylated tau217 (p-tau217). However, its associations with specific clinical characteristics in DLB remain underexplored. This study aims to investigate the role of plasma p-tau217 in DLB and explore how amyloid co-pathology contributes to its clinical heterogeneity. 23 patients diagnosed with DLB at the Movement Disorder Unit, University Hospital of Padova, were classified as biomarker-positive or biomarker-negative based on plasma ptau-217 levels, Amyloid-PET, or CSF analyses. Neuropsychological data assessing cognitive performance across the most affected domains in DLB were also collected. Results revealed that biomarker-positive patients performed significantly worse on the MoCA-MIS and memory-related tests compared to biomarker-negative patients, while p-tau217 levels showed significant negative correlations with the MoCA, MoCA-MIS, and memory Z composite scores. These findings indicate that elevated p-tau217 levels significantly influence memory performance, emphasizing its clinical implication as a non-invasive biomarker for detecting AD related co-pathology in DLB. Identifying patients with mixed DLB-AD pathology proves crucial in refining diagnosis, prognosis, and therapeutic strategies by informing early interventions and potentially supporting inclusion in future clinical trials targeting amyloid pathology.