The brain-first vs. body-first model of Parkinson's disease with comparison to alternative models.
Autonomic
Dopamine
Natural history
Parkinson’s disease
Pathogenesis
Postmortem
Journal
Journal of neural transmission (Vienna, Austria : 1996)
ISSN: 1435-1463
Titre abrégé: J Neural Transm (Vienna)
Pays: Austria
ID NLM: 9702341
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
08
03
2023
accepted:
03
04
2023
medline:
22
5
2023
pubmed:
17
4
2023
entrez:
16
4
2023
Statut:
ppublish
Résumé
The ultimate origin of Lewy body disorders, including Parkinson's disease (PD) and Dementia with Lewy bodies (DLB), is still incompletely understood. Although a large number of pathogenic mechanisms have been implicated, accumulating evidence support that aggregation and neuron-to-neuron propagation of alpha-synuclein may be the core feature of these disorders. The synuclein, origin, and connectome (SOC) disease model of Lewy body disorders was recently introduced. This model is based on the hypothesis that in the majority of patients, the first alpha-synuclein pathology arises in single location and spreads from there. The most common origin sites are the enteric nervous system and the olfactory system. The SOC model predicts that gut-first pathology leads to a clinical body-first subtype characterized by prodromal autonomic symptoms and REM sleep behavior disorder. In contrast, olfactory-first pathology leads to a brain-first subtype with fewer non-motor symptoms before diagnosis. The SOC model further predicts that body-first patients are older, more commonly develop symmetric dopaminergic degeneration, and are at increased risk of dementia-compared to brain-first patients. In this review, the SOC model is explained and compared to alternative models of the pathogenesis of Lewy body disorders, including the Braak staging system, and the Unified Staging System for Lewy Body Disorders. Postmortem evidence from brain banks and clinical imaging data of dopaminergic and cardiac sympathetic loss is reviewed. It is concluded that these datasets seem to be more compatible with the SOC model than with those alternative disease models of Lewy body disorders.
Identifiants
pubmed: 37062013
doi: 10.1007/s00702-023-02633-6
pii: 10.1007/s00702-023-02633-6
doi:
Substances chimiques
alpha-Synuclein
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
737-753Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.
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