Parkinsonian disorders constitute a biologically heterogeneous spectrum of progressive neurodegenerative diseases characterized by overlapping motor, cognitive, autonomic, and neuropsychiatric manifestations, thereby complicating early and subtype-specific diagnosis. The transition from conventional clinicopathological classification toward biomarker-driven precision neurology has substantially reshaped contemporary diagnostic paradigms. This systematic review comprehensively evaluates emerging molecular, biochemical, genetic, and neuroimaging biomarkers implicated in idiopathic Parkinson disease and atypical parkinsonian syndromes, including multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy bodies.

Fluid biomarkers analyzed encompass total, oligomeric, and phosphorylated α-synuclein species, α-synuclein seed amplification assays, neurofilament light chain, phosphorylated and total tau, amyloid-β42/40 ratio, glial fibrillary acidic protein, ubiquitin carboxyl-terminal hydrolase L1, lysosomal enzymes, inflammatory cytokines, microRNAs, exosomal neuronal proteins, and metabolomic signatures derived from cerebrospinal fluid, plasma, saliva, and peripheral tissues. Genetic biomarkers involving LRRK2, SNCA, PRKN, PINK1, DJ-1, VPS35, and GBA mutations are critically appraised for their diagnostic and pathogenetic significance.

Advanced neuroimaging modalities reviewed include dopamine transporter single-photon emission computed tomography, fluorodopa and fluorodeoxyglucose positron-emission tomography, tau positron-emission tomography, susceptibility-weighted imaging, diffusion tensor imaging, neuromelanin magnetic resonance imaging, quantitative susceptibility mapping, and functional connectivity analyses. Emerging evidence suggests that multimodal biomarker integration enhances diagnostic accuracy, disease stratification, prognostication, and therapeutic targeting. Nevertheless, limitations related to assay standardization, longitudinal reproducibility, cohort heterogeneity, and translational scalability continue to impede widespread clinical implementation. Collectively, these advances highlight the convergence of molecular neuroscience and precision medicine in redefining the future diagnostic architecture of Parkinsonian disorders and facilitating personalized therapeutic strategies.

Birupaksha Biswas, MD, is a clinical pathologist, physician-scientist, and translational researcher affiliated with the department of pathology, Burdwan Medical College and Kakdwip Superspeciality Hospital, West Bengal, India. His academic interests span molecular oncology, hematopathology, critical care medicine, regenerative therapeutics, digital pathology, and precision diagnostics. He has authored more than 80 peer-reviewed publications and over 13 academic books, contributing extensively to oncopathology, biomarker discovery, stem-cell therapeutics, and evidence synthesis. He has delivered keynote and invited lectures at international scientific meetings and serves as an active reviewer for reputed journals. A member of the European Hematology Association and the Asian Society of Digital Pathology, he is presently pursuing advanced training in Critical Care Medicine through programs accredited by the Royal College of Physicians (UK) and Health Education England.