Title | Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Iturria-Medina Y, Sotero RC, Toussaint PJ, Mateos-Pérez JM, Evans AC |
Corporate Authors | Alzheimer’s Disease Neuroimaging Initiative |
Journal | Nat Commun |
Volume | 7 |
Pagination | 11934 |
Date Published | 2016 06 21 |
ISSN | 2041-1723 |
Keywords | Aged, Alzheimer Disease, Amyloid beta-Peptides, Biomarkers, Blood Proteins, Brain, Brain Mapping, Cerebrovascular Circulation, Cognitive Dysfunction, Disease Progression, Female, Glucose, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Models, Statistical, Multivariate Analysis, Neuroimaging, Positron-Emission Tomography, tau Proteins |
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. |
DOI | 10.1038/ncomms11934 |
Alternate Journal | Nat Commun |
PubMed ID | 27327500 |
PubMed Central ID | PMC4919512 |
Grant List | P50 AG005136 / AG / NIA NIH HHS / United States P50 AG005142 / AG / NIA NIH HHS / United States U01 AG024904 / AG / NIA NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States |
Related Institute:
Brain Health Imaging Institute (BHII)