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Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis

Author

Listed:
  • Y. Iturria-Medina

    (McConnell Brain Imaging Centre, Montreal Neurological Institute
    Ludmer Centre for NeuroInformatics and Mental Health)

  • R. C. Sotero

    (University of Calgary)

  • P. J. Toussaint

    (McConnell Brain Imaging Centre, Montreal Neurological Institute
    Ludmer Centre for NeuroInformatics and Mental Health)

  • J. M. Mateos-Pérez

    (McConnell Brain Imaging Centre, Montreal Neurological Institute
    Ludmer Centre for NeuroInformatics and Mental Health)

  • A. C. Evans

    (McConnell Brain Imaging Centre, Montreal Neurological Institute
    Ludmer Centre for NeuroInformatics and Mental Health)

Abstract

Multifactorial mechanisms underlying late-onset Alzheimer’s disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD–abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system’s integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11934
    DOI: 10.1038/ncomms11934
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    Cited by:

    1. Lazaro M Sanchez-Rodriguez & Yasser Iturria-Medina & Erica A Baines & Sabela C Mallo & Mehdy Dousty & Roberto C Sotero & on behalf of The Alzheimer’s Disease Neuroimaging Initiative, 2018. "Design of optimal nonlinear network controllers for Alzheimer's disease," PLOS Computational Biology, Public Library of Science, vol. 14(5), pages 1-24, May.
    2. 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.
    3. Stacy A. Hussong & Andy Q. Banh & Candice E. Skike & Angela O. Dorigatti & Stephen F. Hernandez & Matthew J. Hart & Beatriz Ferran & Haneen Makhlouf & Maria Gaczynska & Pawel A. Osmulski & Salome A. M, 2023. "Soluble pathogenic tau enters brain vascular endothelial cells and drives cellular senescence and brain microvascular dysfunction in a mouse model of tauopathy," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Patrick S. Hosford & Jack A. Wells & Shereen Nizari & Isabel N. Christie & Shefeeq M. Theparambil & Pablo A. Castro & Anna Hadjihambi & L. Felipe Barros & Iván Ruminot & Mark F. Lythgoe & Alexander V., 2022. "CO2 signaling mediates neurovascular coupling in the cerebral cortex," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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