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

TitleEarly role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis.
Publication TypeJournal Article
Year of Publication2016
AuthorsIturria-Medina Y, Sotero RC, Toussaint PJ, Mateos-Pérez JM, Evans AC
Corporate AuthorsAlzheimer’s Disease Neuroimaging Initiative
JournalNat Commun
Volume7
Pagination11934
Date Published2016 06 21
ISSN2041-1723
KeywordsAged, 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.

DOI10.1038/ncomms11934
Alternate JournalNat Commun
PubMed ID27327500
PubMed Central IDPMC4919512
Grant ListP50 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)

Weill Cornell Medicine
Department of Radiology
525 East 68th Street New York, NY 10065