Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis.
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.
Department of Neurology &Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, Quebec, Canada H3A 2B4.|Ludmer Centre for NeuroInformatics and Mental Health, Montreal, Quebec, Canada H3A 2B4.
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Iturria-Medina
Department of Radiology and Hotchkiss Brain institute, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
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Sotero
Department of Neurology &Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, Quebec, Canada H3A 2B4.|Ludmer Centre for NeuroInformatics and Mental Health, Montreal, Quebec, Canada H3A 2B4.
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PJ
Toussaint
Department of Neurology &Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, Quebec, Canada H3A 2B4.|Ludmer Centre for NeuroInformatics and Mental Health, Montreal, Quebec, Canada H3A 2B4.
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JM
Mateos-Pérez
Department of Neurology &Neurosurgery, McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, Quebec, Canada H3A 2B4.|Ludmer Centre for NeuroInformatics and Mental Health, Montreal, Quebec, Canada H3A 2B4.
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Evans
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001798:Blood Proteins / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D001931:Brain Mapping; D002560:Cerebrovascular Circulation; D060825:Cognitive Dysfunction / Q000097:blood / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D059906:Neuroimaging; D049268:Positron-Emission Tomography; D016875:tau Proteins / Q000097:blood / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D001798:Blood Proteins; C054369:MAPT protein, human; D016875:tau Proteins; D005947:Glucose