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Despite this biological complexity, current diagnosis and staging of PD remain largely anchored in clinical manifestations. Neuronal aggregation of misfolded \u03b1\u2010synuclein and degeneration of the nigrostriatal dopaminergic system precede the onset of motor symptoms; this phase is termed the prodromal stage of PD. Therefore, clinically based frameworks inherently limit early detection and stratification. In contrast, Alzheimer's disease has undergone a paradigm shift toward a biomarker\u2010driven biological definition, prompting a similar reappraisal of PD as a biologically defined disease continuum. Accumulating evidence indicates that pathological \u03b1\u2010synuclein aggregates in PD extend beyond the central nervous system and exhibit heterogeneous patterns of initiation and propagation. Methodological advances have expanded the capacity to detect these pathological species in\u00a0vivo. In particular, \u03b1\u2010synuclein seed amplification assays (SAA) enable the detection of seeding\u2010competent \u03b1\u2010synuclein species in biofluids and peripheral tissues, providing evidence consistent with \u03b1\u2010synuclein pathology; however, SAA should not be interpreted as a direct reflection of disease stage, progression, or pathological burden. Furthermore, the development of \u03b1\u2010synuclein positron emission tomography ligands offers the prospect of non\u2010invasive visualization of pathological burden, spatial distribution, and longitudinal target engagement, thereby complementing biofluid\u2010based approaches. Together, these biomarker advances underpin emerging biologically anchored classification and staging frameworks, such as the SynNeurGe system and the Neuronal \u03b1\u2010Synuclein Disease Integrated Staging System (NSD\u2010ISS). These frameworks integrate \u03b1\u2010synuclein pathology, neurodegeneration, genetic background, and clinical features to define disease identity and progression across asymptomatic, prodromal, and manifest stages. We synthesize recent advances in \u03b1\u2010synuclein\u2013centered biomarkers and biological staging frameworks and discuss how their convergence is beginning to reshape PD from a primarily symptom\u2010based diagnosis toward a molecularly grounded disease continuum. This transition has the potential to complement clinically defined PD with biologically informed perspectives.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70491-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70491","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T11:56:12Z","timestamp":1781006172000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Biological Framework for Parkinson's Disease: Advances in \u03b1\u2010Synuclein\u2013Centered Biomarkers 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