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Patient-specific models link neurotransmitter receptor mechanisms with motor and visuospatial axes of Parkinson’s disease

Author

Listed:
  • Ahmed Faraz Khan

    (Montreal Neurological Institute, McGill University
    Montreal Neurological Institute
    Ludmer Centre for Neuroinformatics & Mental Health)

  • Quadri Adewale

    (Montreal Neurological Institute, McGill University
    Montreal Neurological Institute
    Ludmer Centre for Neuroinformatics & Mental Health)

  • Sue-Jin Lin

    (Montreal Neurological Institute, McGill University
    Montreal Neurological Institute
    Ludmer Centre for Neuroinformatics & Mental Health)

  • Tobias R. Baumeister

    (Montreal Neurological Institute, McGill University
    Montreal Neurological Institute
    Ludmer Centre for Neuroinformatics & Mental Health)

  • Yashar Zeighami

    (Montreal Neurological Institute, McGill University
    McGill University)

  • Felix Carbonell

    (Biospective Inc)

  • Nicola Palomero-Gallagher

    (Research Centre Jülich
    Heinrich-Heine University
    Medical Faculty, RWTH Aachen, and JARA - Translational Brain Medicine)

  • Yasser Iturria-Medina

    (Montreal Neurological Institute, McGill University
    Montreal Neurological Institute
    Ludmer Centre for Neuroinformatics & Mental Health)

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.

Suggested Citation

  • Ahmed Faraz Khan & Quadri Adewale & Sue-Jin Lin & Tobias R. Baumeister & Yashar Zeighami & Felix Carbonell & Nicola Palomero-Gallagher & Yasser Iturria-Medina, 2023. "Patient-specific models link neurotransmitter receptor mechanisms with motor and visuospatial axes of Parkinson’s disease," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41677-w
    DOI: 10.1038/s41467-023-41677-w
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    References listed on IDEAS

    as
    1. Y. Iturria-Medina & R. C. Sotero & P. J. Toussaint & J. M. Mateos-Pérez & A. C. Evans, 2016. "Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis," Nature Communications, Nature, vol. 7(1), pages 1-14, September.
    2. Fang-Cheng Yeh & Timothy D Verstynen & Yibao Wang & Juan C Fernández-Miranda & Wen-Yih Isaac Tseng, 2013. "Deterministic Diffusion Fiber Tracking Improved by Quantitative Anisotropy," PLOS ONE, Public Library of Science, vol. 8(11), pages 1-1, November.
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