Amyloid and Tau Co-pathology in Parkinson Disease and Atypical Parkinsonism

We performed a narrative review of the literature of amyloid and tau co-pathology in Parkinson Disease and atypical parkinsonism in Pubmed database, including articles published between January 2020 to July 2025.

In the last decade, different multicenter research efforts have worked to improve the accuracy of clinical-pathological diagnosis in neurogenerative disease. In this search, growing evidence from neuropathology, neuroimaging and fluid biomarkers have highlighted the role of Alzheimer's disease (AD) co-pathology in Parkinson's disease (PD) and atypical parkinsonism (AP) disorders potentially affecting progression, motor phenotype and cognitive status. Regarding studies of structural and functional imaging evidencing the presence of Amyloid-β (Aβ), tau, as co-pathologies contribute to α-synuclein-related profile of cortical atrophy, network disruption, as well as clinical heterogeneity in PD and AP disorders. In AP fluid biomarkers have shown limited diagnostic accuracy. Neuropathological evidence from systematic post-mortem surveys confirmed that diffuse and neuritic Aβ plaques are uncommon in non-demented PD (10%), intermediate in PD-dementia (30-40%), and frequent in Dementia with Lewy Bodies (60-80%). The evidence in PD and DLB showed that Aß fluid biomarkers may predict clinical trajectory and cognitive decline, while Aβ-imaging would help stratifying patients and directing therapeutic pipeline designs. In AP disorders, including progressive supranuclear palsy and corticobasal degeneration, a combined multimodal assessment of molecular imaging, structural and functional magnetic resonance with fluid biomarkers shall guarantee future differential diagnosis and prediction of clinical outcomes. Although there are no currently accepted biomarkers for PD or AP, the recent design of plasma tau biomarkers and seed-amplification assays are promising approaches which are also reviewed here.