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Biological diagnosis and staging or classification systems in PD.

Owing to rapidly emerging evidence on neurodegeneration biology, there is raising interest in developing disease staging and/or classification systems. Against this background, key opinion leaders across the International Parkinson and Movement Disorder Society (MDS) released astatement on biological definition, staging and classification of Parkinson’ s Disease (PD)in the Movement Disorders journal. This follows an MDS meeting of international PD experts and patient representativesin April 2023. Starting with the definitions and intended uses of common terms (i.e.“disease”,“disease classification”, “disease staging”,“rating scale”), Cardoso et al., state that a well-developed staging system plays a pivotal role in detecting PD in the earliest stages and providing effective communication with patients about disease severity, expected outcomes, and optimal management. They agree on the need of establishing the biological definition of PD to develop a global biological staging system which captures multiple disease-triggering mechanisms likely contributing to PD (1). Although α-synuclein aggregation is considered by most experts the major biological event underlying PD and is detectable in vivo by seed amplification assays using cerebrospinal fluid, saliva, blood, colonic mucosa, and skin, the statement highlights that seeding tests do not necessarily reflect α-synuclein aggregation in PD patients’ brain. Since α-synuclein is not present in all PD forms (as exemplified with PRKN-PD), addressing the genetic status is also important. The authors finally emphasize that progresses in the biomarker field will likely fuel a comprehensive biological and clinical staging tool that should incorporate motor and non-motor PD features, be accessible regardless of geographical/economical limitations, and prompt disease-modifying treatment development.

Key Points:

  • A global staging system should take into account both biomarkers and motor/non-motor features with prognostic power.
  • Prior to disease definition, it is crucial to address the genetic status of PD.
  • Importantly, a PD definition, staging and classification system should be accessible without geographical and economical limits.
  • As regards clinical trials, a staging system should correctly identify a homogeneous group of patients with sensitive assays and biomarkers correlated to the changes in the underlying biology.
  • Biological definition of a disease must be useful to distinguish it from conditions sharing clinical similarities. Specifically, among synucleinopathies, it should be able to distinguish PD from DLB, MSA and RBD, i.e. the common prodromal condition.


  1. Cardoso F, Goetz CG, Mestre TA, Sampaio C, Adler CH, Berg D, Bloem BR, Burn DJ, Fitts MS, Gasser T, Klein C, de Tijssen MAJ, Lang AE, Lim SY, Litvan I, Meissner WG, Mollenhauer B, Okubadejo N, Okun MS, Postuma RB, Svenningsson P, Tan LCS, Tsunemi T, Wahlstrom-Helgren S, Gershanik OS, Fung VSC, Trenkwalder C. A Statement of the MDS on Biological Definition, Staging, and Classification of Parkinson's Disease. MovDisord. 2023 Dec 13. doi: 10.1002/mds.29683.
  2. Chahine LM, Merchant K, Siderowf A, Sherer T, Tanner C, Marek K, Simuni T. Proposal for a Biologic Staging System of Parkinson's Disease. J Parkinsons Dis. 2023;13(3):297-309. doi: 10.3233/JPD-225111. PMID: 37066922; PMCID: PMC10200239.
  3. Mestre TA, Fereshtehnejad SM, Berg D, et al. Parkinson’s disease subtypes: critical appraisal and recommendations. J Parkinsons Dis 2021;11(2):395–404.

Anastasia Bougea, National and Kapodistrian University of Athens 1st Division of Neurology, Athens, Greece

Publish on behalf of the Scientific Panel on Movement disorders