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Brain-First versus Gut-First Parkinson's Disease: A Hypothesis
Per Borghammer1,2, Nathalie Van Den Berge2
1Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark.
Journal of Parkinson'S Disease
|September 10, 2019
Summary
Parkinson's disease may have two subtypes: one starting in the peripheral nervous system (PNS) and linked to REM sleep behavior disorder (RBD), and another starting in the central nervous system (CNS) without early RBD.
Area of Science:
- Neurology
- Neuroscience
- Pathology
Background:
- Parkinson's disease (PD) is a heterogeneous disorder.
- Alpha-synuclein aggregation is a key factor in PD pathogenesis.
- The hypothesis of PD originating in the peripheral nervous system (PNS) and spreading to the central nervous system (CNS) is not universally supported by neuropathological findings.
Purpose of the Study:
- To propose a new hypothesis dividing PD into PNS-first and CNS-first subtypes.
- To explain discrepant findings in PD neuropathology.
- To provide a framework for future research into PD etiopathogenesis.
Main Methods:
- Review of neuropathological studies.
- Analysis of in vivo imaging studies in RBD-positive and RBD-negative patients.
- Histological evidence review.
Main Results:
- A hypothesis of two PD subtypes: PNS-first and CNS-first.
- PNS-first PD is associated with prodromal REM sleep behavior disorder (RBD) and early autonomic damage.
- CNS-first PD is typically RBD-negative and characterized by early nigrostriatal dopaminergic dysfunction.
Conclusions:
- The proposed subtypes offer a potential explanation for varied PD presentations and neuropathological findings.
- This framework may guide future research into the distinct origins and progression of Parkinson's disease.