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

The Alzheimer's Disease Neuroimaging Initiative

Research output: Contribution to journalArticle

163 Citations (Scopus)

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 languageEnglish (US)
Article number11934
JournalNature Communications
Volume7
DOIs
StatePublished - Jun 21 2016

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Blood Vessels
Alzheimer Disease
Biomarkers
biomarkers
Disease Progression
brain
Brain
abnormalities
progressions
integrity
Memory Disorders
Amyloid
Neuroimaging
Cerebrospinal Fluid
cerebrospinal fluid
cardiovascular system
Cerebrospinal fluid
proteins
Proteins
metabolism

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis. / The Alzheimer's Disease Neuroimaging Initiative.

In: Nature Communications, Vol. 7, 11934, 21.06.2016.

Research output: Contribution to journalArticle

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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.",
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