Prodromal Parkinson disease subtypes — key to understanding heterogeneity
Abstract
In Parkinson disease (PD), pathological processes and neurodegeneration begin long before the cardinal motor symptoms develop and enable clinical diagnosis. In this prodromal phase, risk and prodromal markers can be used to identify individuals who are likely to develop PD, as in the recently updated International Parkinson and Movement Disorders Society research criteria for prodromal PD. However, increasing evidence suggests that clinical and prodromal PD are heterogeneous, and can be classified into subtypes with different clinical manifestations, pathomechanisms and patterns of spatial and temporal progression in the CNS and PNS. Genetic, pathological and imaging markers, as well as motor and non-motor symptoms, might define prodromal subtypes of PD. Moreover, concomitant pathology or other factors, including amyloid-β and tau pathology, age and environmental factors, can cause variability in prodromal PD. Patients with REM sleep behaviour disorder (RBD) exhibit distinct patterns of α-synuclein pathology propagation and might indicate a body-first subtype rather than a brain-first subtype. Identification of prodromal PD subtypes and a full understanding of variability at this stage of the disease is crucial for early and accurate diagnosis and for targeting of neuroprotective interventions to ensure efficacy.
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CNS diseases often present with a wide range of symptoms that vary among individuals, making it challenging to develop standardized diagnostic criteria and treatment approaches.
“CNS diseases often present with a wide range of symptoms that vary among individuals. This heterogeneity makes it challenging to develop standardized diagnostic criteria and treatment approaches [21, 22].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [21]
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- Authors
- Berg, D., Borghammer, P., Fereshtehnejad, S.-M., Heinzel, S., Horsager, J., Schaeffer, E., & Postuma, R. B.
- Affiliations
- Christian-Albrechts-Universität zu Kiel (DE)
- Aarhus University (DK)
- University of Ottawa (CA)
- Aarhus University Hospital (DK)
- Hôpital du Sacré-Cœur de Montréal (CA)
- Corresponding author
- Berg, Daniela
- ORCID
- Venue
- Nature Reviews Neurology
- Published
- 2021-04-20
- Volume
- 17
- Issue
- 6
- Pages
- 349-361
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- OpenAlex
- W3153424147
- Cited by
- 409
- References
- 13
- Citations by year
- 2026: 51 · 2025: 106 · 2024: 89 · 2023: 83 · 2022: 66 · 2021: 14
- FWCI
- 8.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Lundbeckfonden (R276‐2018‐294)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- prodromal Parkinson's disease, disease heterogeneity, prodromal markers, REM sleep behavior disorder, amyloid-beta, tau pathology, non-motor symptoms, early diagnosis, neurodegeneration
- MeSH terms
- Brain, Humans, Parkinson Disease, Biomarkers, REM Sleep Behavior Disorder, Neuroimaging, Prodromal Symptoms
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