Fluid biomarkers in atypical Parkinsonism: Current state and future perspectives

Diagnosing Atypical Parkinsonian Syndromes (APS) may be challenging due to overlapping clinical features of Parkinson’s disease (PD), and the lack of pathognomonic diagnostic tests. Fluid biomarkers can be useful tools that make it easier to identify and track diferent APS. Objectives: this narrative review aim to update the current state of fuid biomarker research in APS and their potential implications in clinical practice. A comprehensive literature search was conducted in PubMed and Scopus using the following terms: “Aβ42 amyloid beta with 42 amino acids’’, “ alpha-synuclein’’, “Atypical Parkinso nian Syndromes’’, “corticobasaldegeneration’’, “C reactive protein’’, “cerebrospinal fuid’’, “dementia with Lewy bodies’’, “multiple system atrophy’’, “neuroflament light, oligomericαsyn, phosphorylated α –syn’’, “tau phosphorylated at threonine 181’’, “progressive supranuclear palsy’’, “Seeding Amplifcation Assay’’, “t-tau; total tau”. The lack of high-afnity α-syn antibodies and ligands may contribute to α-syn’s low efcacy as a diagnostic biomarker of APS. Cerebrospinal fuid (CSF) biomarkers refecting Alzheimer pathology, axonal damage (neuroflament light chain) add valuable diagnostic and prog nostic information in the neurochemical characterization of APS. Infammatoryand microRNAs markers need to be further validated before their clinical use. Seeding Amplifcation Assays (SAA), despite their high sensitivity and specifcity, are at this point used only as a research tool, and they are not quantitative or refective of disease severity. Biomarker research for early identifcation and prognosis of APS patients requires multicenter collaboration, validation, and AI-based diagnostics, despite immature biological classifcation systems.