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Patient-specific models link neurotransmitter receptor mechanisms with motor and visuospatial axes of Parkinson’s disease
- Source :
- Nature Communications, Vol 14, Iss 1, Pp 1-17 (2023)
- Publication Year :
- 2023
- Publisher :
- Nature Portfolio, 2023.
-
Abstract
- Abstract Parkinson’s disease involves multiple neurotransmitter systems beyond the classical dopaminergic circuit, but their influence on structural and functional alterations is not well understood. Here, we use patient-specific causal brain modeling to identify latent neurotransmitter receptor-mediated mechanisms contributing to Parkinson’s disease progression. Combining the spatial distribution of 15 receptors from post-mortem autoradiography with 6 neuroimaging-derived pathological factors, we detect a diverse set of receptors influencing gray matter atrophy, functional activity dysregulation, microstructural degeneration, and dendrite and dopaminergic transporter loss. Inter-individual variability in receptor mechanisms correlates with symptom severity along two distinct axes, representing motor and psychomotor symptoms with large GABAergic and glutamatergic contributions, and cholinergically-dominant visuospatial, psychiatric and memory dysfunction. Our work demonstrates that receptor architecture helps explain multi-factorial brain re-organization, and suggests that distinct, co-existing receptor-mediated processes underlie Parkinson’s disease.
- Subjects :
- Science
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 14
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.99f9f45ced0d425fbc90cae72e8a2585
- Document Type :
- article
- Full Text :
- https://doi.org/10.1038/s41467-023-41677-w