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

Authors

Y. Iturria-Medina, McConnell Brain Imaging Centre
R. C. Sotero, Hotchkiss Brain Institute
P. J. Toussaint, McConnell Brain Imaging Centre
J. M. Mateos-Pérez, McConnell Brain Imaging Centre
A. C. Evans, McConnell Brain Imaging Centre
Michael W. Weiner, University of California, San Francisco
Paul Aisen, University of California, San Diego
Ronald Petersen, Mayo Clinic
Clifford R. Jack, Mayo Clinic
William Jagust, University of California, Berkeley
John Q. Trojanowki, University of Pennsylvania
Arthur W. Toga, University of Southern California
Laurel Beckett, University of California, Davis
Robert C. Green, Brigham and Women's Hospital
Andrew J. Saykin, Indiana University Bloomington
John Morris, Washington University in St. Louis
Leslie M. Shaw, University of Pennsylvania
Zaven Khachaturian, University of California, San Diego
Greg Sorensen, Siemens AG
Lew Kuller, University of Pittsburgh
Marc Raichle, Washington University in St. Louis
Steven Paul, Cornell University
Peter Davies, Albert Einstein College of Medicine of Yeshiva University
Howard Fillit, Alzheimer's Drug Discovery Foundation
Franz Hefti, Acumen Pharmaceuticals
Davie Holtzman, Washington University in St. Louis
M. Marcel Mesulam, Northwestern University
William Potter, National Institute of Mental Health (NIMH)
Peter Snyder, Brown University
Adam Schwartz, Eli Lilly and Company
Tom Montine, University of Washington
Ronald G. Thomas, University of California, San Diego

Document Type

Article

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.

Publication Date

6-21-2016

Publication Title

Nature Communications

E-ISSN

20411723

Volume

7

PubMed ID

27327500

Digital Object Identifier (DOI)

10.1038/ncomms11934

Recommended Citation

Iturria-Medina, Y.; Sotero, R. C.; Toussaint, P. J.; Mateos-Pérez, J. M.; Evans, A. C.; Weiner, Michael W.; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Khachaturian, Zaven; Sorensen, Greg; Kuller, Lew; Raichle, Marc; Paul, Steven; Davies, Peter; Fillit, Howard; Hefti, Franz; Holtzman, Davie; Mesulam, M. Marcel; Potter, William; Snyder, Peter; Schwartz, Adam; Montine, Tom; and Thomas, Ronald G., "Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis" (2016). Neurology. 859.
https://scholar.barrowneuro.org/neurology/859