4.6 Article

Multiplex Connectome Changes across the Alzheimer's Disease Spectrum Using Gray Matter and Amyloid Data

Journal

CEREBRAL CORTEX
Volume 32, Issue 16, Pages 3501-3515

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhab429

Keywords

Alzheimer's disease; amyloid; gray matter; multilayer brain networks; multiplex connectome

Categories

Funding

  1. Swedish Research Council [2018-02201]
  2. Center for Medical Innovation [20200695]
  3. Senior Researcher Position Karolinska Institute grant
  4. Gamla Tjanarinnor [2020-01016]
  5. Stohnes
  6. National Institutes of Health [U01 AG024904]
  7. Department of Defense [W81XWH12-2-0012]
  8. National Institute on Aging
  9. National Institute of Biomedical Imaging and Bioengineering
  10. Alzheimer's Association
  11. Alzheimer's Drug Discovery Foundation
  12. BioClinica, Inc.
  13. Biogen Idec Inc.
  14. Bristol-Myers Squibb Company
  15. Eisai Inc.
  16. Elan Pharmaceuticals, Inc.
  17. Eli Lilly and Company
  18. F. Hoffmann -LaRoche Ltd
  19. Genentech, Inc.
  20. GEHealthcare
  21. Innogenetics, N.V.
  22. IXICO Ltd
  23. Janssen Alzheimer Immunotherapy Research & Development, LLC.
  24. Johnson & Johnson Pharmaceutical Research & Development LLC.
  25. Medpace, Inc.
  26. Merck Co., Inc.
  27. Meso Scale Diagnostics, LLC.
  28. NeuroRx Research
  29. Novartis Pharmaceuticals Corporation
  30. Pfizer Inc.
  31. Piramal Imaging
  32. Servier
  33. Synarc Inc.
  34. Takeda Pharmaceutical Company
  35. Canadian Institutes of Health Research
  36. Vinnova [2018-02201] Funding Source: Vinnova
  37. Swedish Research Council [2018-02201] Funding Source: Swedish Research Council

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This study integrates amyloid PET and gray matter MRI data into a multiplex connectome to explore the interaction between amyloid-beta pathology and brain atrophy in Alzheimer's disease (AD). The findings offer new insights into the pathological processes of AD beyond traditional graph theory analyses based on single brain networks.
The organization of the Alzheimer's disease (AD) connectome has been studied using graph theory using single neuroimaging modalities such as positron emission tomography (PET) or structural magnetic resonance imaging (MRI). Although these modalities measure distinct pathological processes that occur in different stages in AD, there is evidence that they are not independent from each other. Therefore, to capture their interaction, in this study we integrated amyloid PET and gray matter MRI data into a multiplex connectome and assessed the changes across different AD stages. We included 135 cognitively normal (CN) individuals without amyloid-beta pathology (A beta-) in addition to 67 CN, 179 patients with mild cognitive impairment (MCI) and 132 patients with AD dementia who all had A beta pathology (A beta+) from the Alzheimer's Disease Neuroimaging Initiative. We found widespread changes in the overlapping connectivity strength and the overlapping connections across A beta-positive groups. Moreover, there was a reorganization of the multiplex communities in MCI A beta + patients and changes in multiplex brain hubs in both MCI A beta + and AD A beta + groups. These findings offer a new insight into the interplay between amyloid-beta pathology and brain atrophy over the course of AD that moves beyond traditional graph theory analyses based on single brain networks.

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