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Brain-derived and circulating vesicle profiles indicate neurovascular unit dysfunction in early Alzheimer's disease.

Authors
  • Gallart-Palau, Xavier1
  • Serra, Aida1
  • Hase, Yoshiki2
  • Tan, Chee Fan1
  • Chen, Christopher P3, 4
  • Kalaria, Raj N2
  • Sze, Siu Kwan1
  • 1 School of Biological Sciences, Nanyang Technological University, Singapore, Singapore. , (Singapore)
  • 2 Institute of Neuroscience, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK.
  • 3 Memory, Aging and Cognition Centre, National University Health System, Singapore, Singapore. , (Singapore)
  • 4 Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. , (Singapore)
Type
Published Article
Journal
Brain Pathology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Sep 01, 2019
Volume
29
Issue
5
Pages
593–605
Identifiers
DOI: 10.1111/bpa.12699
PMID: 30629763
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Vascular factors that reduce blood flow to the brain are involved in apparition and progression of dementia. We hypothesized that cerebral hypoperfusion (CH) might alter the molecular compositions of brain intercellular communication mechanisms while affecting the neurovascular unit in preclinical and clinical human dementias. To test that hypothesis, mice were subjected to bilateral common carotid stenosis (BCAS) and the molecular compositions of brain-derived and circulating extracellular vesicles (EVs) were assessed. Murine brain vesicle profiles were then analyzed in parallel with brain EVs from post-mortem subjects affected by preclinical Alzheimer's Disease (AD) and mixed dementias. Brain EVs were identified with molecular mediators of hypoxia responses, neuroprotection and neurotoxicity in BCAS mice, patterns also partially resembled by subjects with preclinical AD and mixed dementias. Together these findings indicate that brain EVs represent a promising source of therapeutic targets and circulating markers of neurovascular insult in idiopathic dementias. Furthermore, the results obtained generate novel and compelling hypotheses about the molecular involvement of the vascular component in the etiology of human dementias. © 2019 International Society of Neuropathology.

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