α-synuclein biomarker assays: bridging research and patient care

The discovery that α-synuclein can be detected in peripheral tissues of patients with Parkinson's disease and other synucleinopathies spurred the development of biomarker assays, including the α-synuclein seed amplification assay for CSF and immunofluorescence detection of dermal phosphorylated-α-synuclein. These tools aim to identify pathological α-synuclein changes, even at the early stages of disease, with the goal of eventually enabling differentiation of Parkinson's disease from other neurodegenerative disorders, including tauopathies. α-synuclein biomarkers add a biological component to the traditional clinical diagnosis of Parkinson's disease, with potential for development of complementary clinical and pathobiological frameworks for Parkinson's disease and related movement disorders. However, use of existing α-synuclein biomarkers is restricted to research settings due to variable sensitivity and specificity, restricted availability of neuropathological data for validation, and scarcity of longitudinal studies. Addressing these limitations is crucial for advancing clinical and biological disease definitions, which will be essential for the development of disease-modifying therapies.