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

Publication Type	Academic Article
Authors	Iturria-Medina Y, Sotero R, Toussaint P, Mateos-Pérez J, Evans A
Journal	Nat Commun
Volume	7
Pagination	11934
Date Published	06/21/2016
ISSN	2041-1723
Keywords	Alzheimer Disease, Brain, Cognitive Dysfunction, Image Interpretation, Computer-Assisted, Models, Statistical
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
PubMed ID	27327500
PubMed Central ID	PMC4919512