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

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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Publication Details

Journal
Movement Disorders
Published
2026-05-22
DOI
https://doi.org/10.1002/mds.70324
Primary Topic
Parkinson's Disease Mechanisms and Treatments
Type
article
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article

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

Michele Matarazzo, Jennifer G. Goldman, Inas Elsayed, Per Svenningsson et al.
Movement Disorders
Parkinson's Disease Mechanisms and Treatments
article

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

Michele Matarazzo, Jennifer G. Goldman, Inas Elsayed, Per Svenningsson, Yue Huang, Jeffrey H. Kordower, Per Borghammer, Lorraine V. Kalia, Katja Lohmann, Daniela Berg
article en

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.

Movement Disorders
University College Dublin (IE), Barrow Neurological Institute (US), University Health Network (CA), University of Toronto (CA), Karolinska Institutet (SE), UNSW Sydney (AU), Christian-Albrechts-Universität zu Kiel (DE), Beijing Tian Tan Hospital (CN), University of Chicago Medical Center (US), Occupational Cancer Research Centre (CA), HM Hospitales (ES), University Hospital HM Puerta del Sur (ES), Lundbeck Foundation (DK), Krembil Research Institute, Arizona State University (US), University of Gezira (SD), University of Lübeck (DE)
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Openalex Percentile: Top 5%
Parkinson's Disease Mechanisms and Treatments
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