Aarhus Universitets segl

The heterogeneity of Parkinson's disease

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisReviewForskningpeer review


  • Ullrich Wüllner, University Clinic Bonn and German Center for Neurodegenerative Diseases (DZNE)
  • ,
  • Per Borghammer
  • Chi-Un Choe, Department of Neurology, Frankfurt am Main, Germany; Department of Neurology, Heidelberg University Hospital, Germany.
  • ,
  • Ilona Csoti, Fachklinik Für Parkinson
  • ,
  • Björn Falkenburger, Technische Universität Dresden
  • ,
  • Thomas Gasser, University of Tübingen and German Center for Neurodegenerative Diseases (DZNE)
  • ,
  • Paul Lingor, Technical University of Munich
  • ,
  • Peter Riederer, Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany.

The heterogeneity of Parkinson's disease (PD), i.e. the various clinical phenotypes, pathological findings, genetic predispositions and probably also the various implicated pathophysiological pathways pose a major challenge for future research projects and therapeutic trail design. We outline several pathophysiological concepts, pathways and mechanisms, including the presumed roles of α-synuclein misfolding and aggregation, Lewy bodies, oxidative stress, iron and melanin, deficient autophagy processes, insulin and incretin signaling, T-cell autoimmunity, the gut-brain axis and the evidence that microbial (viral) agents may induce molecular hallmarks of neurodegeneration. The hypothesis is discussed, whether PD might indeed be triggered by exogenous (infectious) agents in susceptible individuals upon entry via the olfactory bulb (brain first) or the gut (body-first), which would support the idea that disease mechanisms may change over time. The unresolved heterogeneity of PD may have contributed to the failure of past clinical trials, which attempted to slow the course of PD. We thus conclude that PD patients need personalized therapeutic approaches tailored to specific phenomenological and etiologic subtypes of disease.

TidsskriftJournal of neural transmission (Vienna, Austria : 1996)
Sider (fra-til)827-838
Antal sider12
StatusUdgivet - jun. 2023

Bibliografisk note

© 2023. The Author(s).

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