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Network Patterns of Beta-Amyloid Deposition in Parkinson’s Disease

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Abstract

Beta-amyloid (Aβ) in the brain is a key pathological feature of certain neurodegenerative diseases. Recent studies using graph theory have shown that Aβ brain networks are of pathological significance in Alzheimer’s disease (AD). However, the characteristics of Aβ brain networks in Parkinson’s disease (PD) are unknown. In the present study using positron emission tomography (PET) with [11C]-Pittsburgh compound B (PiB), we applied a graph theory–based analysis to assess the topological properties of Aβ brain network in PD patients with and without Aβ burden (PiB-positive and PiB-negative, respectively) and healthy controls with Aβ burden. We found that the PD PiB-positive group demonstrated significantly lower value in global efficiency and modularity compared with PD PiB-negative group. The less robust modular structure indicates the tendency of having increased inter-modular connections than intra-modular connectivity (i.e., reduced segregation). Results of hub organization showed that relative to PD PiB-negative group, different hubs were identified in the PiB-positive group, which were located mainly within the default mode network. Overall, our findings suggest disturbances in Aβ topological organization characterized by abnormal network integration and segregation in PD patients with Aβ burden. The stronger inter-modular connectivity observed in the PD PiB-positive group may suggest the spreading pattern of Aβ between modules in those PD patients with elevated PiB burden, thus providing insight into the beta-amyloidopathy of PD.

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Funding

This work was supported by the Canadian Institutes of Health Research (MOP-136778). Dr. Antonio Strafella is supported by the Canada Research Chair Program.

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Authors and Affiliations

  1. Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada

    Jinhee Kim, Christine Ghadery, Sang Soo Cho, Alexander Mihaescu, Leigh Christopher, Mikaeel Valli, Sylvain Houle & Antonio P. Strafella

  2. Division of Brain, Imaging and Behaviour – Systems Neuroscience, Krembil Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada

    Jinhee Kim, Christine Ghadery, Sang Soo Cho, Alexander Mihaescu, Leigh Christopher, Mikaeel Valli & Antonio P. Strafella

  3. Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada

    Alexander Mihaescu, Mikaeel Valli & Antonio P. Strafella

  4. Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Neurology Division, Department of Medicine, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada

    Antonio P. Strafella

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  1. Jinhee Kim
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  2. Christine Ghadery
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  4. Alexander Mihaescu
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  5. Leigh Christopher
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  7. Sylvain Houle
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  8. Antonio P. Strafella
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Contributions

Study conception and design: JK and APS

Data acquisition: CG and LC

Data analysis: JK and CG

Data interpretation: JK and APS

Manuscript drafting: JK

Manuscript review and critique for important intellectual content: JK, CG, SSC, AM, LC, MV, SH, and APS

Approved version to be published: JK and APS

Corresponding author

Correspondence to Jinhee Kim.

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Kim, J., Ghadery, C., Cho, S.S. et al. Network Patterns of Beta-Amyloid Deposition in Parkinson’s Disease. Mol Neurobiol 56, 7731–7740 (2019). https://doi.org/10.1007/s12035-019-1625-z

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  • DOI: https://doi.org/10.1007/s12035-019-1625-z

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