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- Title
Patient-specific models link neurotransmitter receptor mechanisms with motor and visuospatial axes of Parkinson's disease.
- Authors
Khan, Ahmed Faraz; Adewale, Quadri; Lin, Sue-Jin; Baumeister, Tobias R.; Zeighami, Yashar; Carbonell, Felix; Palomero-Gallagher, Nicola; Iturria-Medina, Yasser
- 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. Neurotransmitter receptor distributions help explain structural and functional brain alterations in Parkinson's disease. Distinct multi-receptor profiles are associated with the severity of motor, and visuospatial, psychiatric and memory symptoms.
- Subjects
PARKINSON'S disease; NEUROTRANSMITTERS; NEUROTRANSMITTER receptors; MEMORY disorders; GRAY matter (Nerve tissue)
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-41677-w