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Peer-reviewedCC BY-NC-NDMovement Disorders

Co‐ and Multi‐Pathologies in Parkinson's Disease: An International Parkinson and Movement Disorder Society Scientific Issues Committee Review

  • Michele Matarazzo1,2
  • Per Borghammer3
  • Inas Elsayed4,5
  • Jennifer G. Goldman6,7
  • Yue Huang8,9
  • Katja Lohmann10
  • Per Svenningsson11
  • Lorraine V. Kalia12,13,14
  • Daniela Berg15
  • Jeffrey H. Kordower16,17
17 affiliations
  1. 1HM CINAC (Centro Integral de Neurociencias Abarca Campal) Hospital Universitario HM Puerta del Sur, HM Hospitales Madrid Spain
  2. 2Instituto de Investigación Sanitaria HM Hospitales Madrid Spain
  3. 3Lundbeck Foundation Parkinson's Disease Research Center (PACE) Aarhus University Aarhus Denmark
  4. 4Faculty of Pharmacy University of Gezira Wad Medani Sudan
  5. 5Systems Biology Ireland, School of Medicine and Medical Science University College Dublin Dublin Ireland
  6. 6Barrow Neurological Institute Phoenix Arizona USA
  7. 7JPG Enterprises Medical Division Chicago Illinois USA
  8. 8Centre for Healthy Brain Aging (CHeBA), Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health UNSW Sydney Sydney Australia
  9. 9Human Brain and Tissue Bank, China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital, Capital Medical University Beijing China
  10. 10Institute of Neurogenetics University of Luebeck Luebeck Germany
  11. 11Karolinska Institutet Stockholm Sweden
  12. 12Division of Neurology, Department of Medicine University of Toronto Toronto Ontario Canada
  13. 13Krembil Research Institute, Toronto Western Hospital University Health Network Toronto Ontario Canada
  14. 14Tanz Centre for Research in Neurodegenerative Diseases University of Toronto Toronto Ontario Canada
  15. 15Department of Neurology, University Hospital Schleswig‐Holstein Campus Kiel and Christian Albrechts‐University of Kiel Kiel Germany
  16. 16ASU‐Banner Neurodegenerative Disease Research Center Tempe Arizona USA
  17. 17School of Life Sciences Arizona State University Tempe Arizona USA
Open at sourceDOICite

Abstract

Parkinson's disease (PD) has been historically defined as a disease of striatal dopamine deficiency secondary to degeneration of dopaminergic neurons in the substantia nigra pars compacta, related to the presence of Lewy bodies and Lewy neurites. Since the discovery of pathogenic variants in the gene encoding α-synuclein, as well as the finding that α-synuclein is a major constituent of Lewy pathology, PD is considered as a prototypical synucleinopathy. However, neuropathological studies consistently show that most people with PD display copathologies, many of which are linked to specific clinical features and outcomes. In this review, we summarize the spectrum and frequency of these co- and multi-pathologies in idiopathic and genetic PD and their impact on disease initiation and progression. Additionally, we also discuss how this multi-pathological landscape may impact biomarker research and the implementation of emerging disease-modifying therapies. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Cite

BibTeXRIS
BibTeX
@article{matarazzo2026multipathologies,
  title = {{Co‐ and Multi‐Pathologies in Parkinson's Disease: An International Parkinson and Movement Disorder Society Scientific Issues Committee Review}},
  author = {Michele Matarazzo and Per Borghammer and Inas Elsayed and Jennifer G. Goldman and Yue Huang and Katja Lohmann and Per Svenningsson and Lorraine V. Kalia and Daniela Berg and Jeffrey H. Kordower},
  journal = {Movement Disorders},
  year = {2026},
  month = may,
  doi = {10.1002/mds.70324},
  url = {https://doi.org/10.1002/mds.70324},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Co‐ and Multi‐Pathologies in Parkinson's Disease: An International Parkinson and Movement Disorder Society Scientific Issues Committee Review
AU  - Michele Matarazzo
AU  - Per Borghammer
AU  - Inas Elsayed
AU  - Jennifer G. Goldman
AU  - Yue Huang
AU  - Katja Lohmann
AU  - Per Svenningsson
AU  - Lorraine V. Kalia
AU  - Daniela Berg
AU  - Jeffrey H. Kordower
PY  - 2026
DA  - 2026/05/22
JO  - Movement Disorders
DO  - 10.1002/mds.70324
UR  - https://doi.org/10.1002/mds.70324
AB  - Parkinson's disease (PD) has been historically defined as a disease of striatal dopamine deficiency secondary to degeneration of dopaminergic neurons in the substantia nigra pars compacta, related to the presence of Lewy bodies and Lewy neurites. Since the discovery of pathogenic variants in the gene encoding α-synuclein, as well as the finding that α-synuclein is a major constituent of Lewy pathology, PD is considered as a prototypical synucleinopathy. However, neuropathological studies consistently show that most people with PD display copathologies, many of which are linked to specific clinical features and outcomes. In this review, we summarize the spectrum and frequency of these co- and multi-pathologies in idiopathic and genetic PD and their impact on disease initiation and progression. Additionally, we also discuss how this multi-pathological landscape may impact biomarker research and the implementation of emerging disease-modifying therapies. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
SN  - 0885-3185
SN  - 1531-8257
ER  -