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.
Original language | English (US) |
---|---|
Article number | 11934 |
Journal | Nature Communications |
Volume | 7 |
DOIs | |
State | Published - Jun 21 2016 |
ASJC Scopus subject areas
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
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In: Nature Communications, Vol. 7, 11934, 21.06.2016.
Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis
AU - Iturria-Medina, Y.
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AU - Johnson, Nancy
AU - Sadowsky, Carl
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AU - Jacobson, Sandra A.
AU - Sirrel, Sherye A.
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AU - Lerner, Alan
AU - Ogrocki, Paula
AU - Hudson, Leon
AU - Fletcher, Evan
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AU - Olichney, John
AU - DeCarli, Charles
AU - Kittur, Smita
AU - Borrie, Michael
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AU - Asthana, Sanjay
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AU - Reeder, Stephanie
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AU - Schwartz, Eben S.
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AU - Williamson, Jeff D.
AU - Garg, Pradeep
AU - Watkins, Franklin
AU - Ott, Brian R.
AU - Querfurth, Henry
AU - Tremont, Geoffrey
AU - Salloway, Stephen
AU - Malloy, Paul
AU - Correia, Stephen
AU - Rosen, Howard J.
AU - Miller, Bruce L.
AU - Mintzer, Jacobo
AU - Spicer, Kenneth
AU - Bachman, David
AU - Finger, Elizabether
AU - Pasternak, Stephen
AU - Rachinsky, Irina
AU - Drost, Dick
AU - Pomara, Nunzio
AU - Hernando, Raymundo
AU - Sarrael, Antero
AU - Schultz, Susan K.
AU - Ponto, Laura L Boles
AU - Shim, Hyungsub
AU - Smith, Karen Elizabeth
AU - Relkin, Norman
AU - Chaing, Gloria
AU - Raudin, Lisa
AU - Smith, Amanda
AU - Fargher, Kristin
AU - Raj, Balebail Ashok
AU - Neylan, Thomas
AU - Grafman, Jordan
AU - Davis, Melissa
AU - Morrison, Rosemary
AU - Hayes, Jacqueline
AU - Finley, Shannon
AU - Friedl, Karl
AU - Fleischman, Debra
AU - Arfanakis, Konstantinos
AU - James, Olga
AU - Massoglia, Dino
AU - Fruehling, J. Jay
AU - Harding, Sandra
AU - Peskind, Elaine R.
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AU - Li, Gail
AU - Yesavage, Jerome A.
AU - Taylor, Joy L.
AU - Furst, Ansgar J.
PY - 2016/6/21
Y1 - 2016/6/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84975882747&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84975882747&partnerID=8YFLogxK
U2 - 10.1038/ncomms11934
DO - 10.1038/ncomms11934
M3 - Article
AN - SCOPUS:84975882747
SN - 2041-1723
VL - 7
JO - Nature Communications
JF - Nature Communications
M1 - 11934
ER -