Abstract: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. The clinical manifestations of PD include motor symptoms, such as bradykinesia, resting tremor, rigidity, and nonmotor symptoms, which include disturbances in sleep, gastrointestinal function, and olfaction. PD misdiagnosis rates have been reported to reach approximately 30%, partly owing to the heterogeneity of parkinsonism with non-PD pathologies, and the differential diagnosis of PD from neurodegenerative diseases such as multiple systemic atrophy (MSA) and progressive supranuclear palsy poses another unmet need. These nonmotor symptoms may emerge more than a decade prior to the onset of motor impairments. Pathologically, PD is characterized by the accumulation of Lewy bodies (LBs), which are composed of misfolded alpha-synuclein, and the early loss of dopaminergic neurons. Recent studies have introduced two biomarker-based systems for PD research: the SyNeurGe system and the neuronal alpha-synuclein disease integrated staging system (Höglinger et al., 2024; Simuni et al., 2024). Misfolded alpha-synuclein has been shown to spread between cells, serving as a template for further alpha-synuclein misfolding. Although the precise etiological role of alphasynuclein in PD has not been fully elucidated, a recent study has revealed heterogeneity in the trajectories of alpha-synuclein pathology in PD and the toxicity of alpha-synuclein especially soluble aggregates (Mastenbroek et al., 2024). Currently, there are several clinical trials targeting alphasynuclein as disease modifying treatments of PD, either by using active or passive immunotherapy, by preventing alpha-synuclein aggregation, or by disaggregation of existing complexes.