Affiliations 

  • 1 Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia
  • 2 Programme of Biomedical Science, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, 50300, Kuala Lumpur, Malaysia
  • 3 Department of Herbal Medicine Resources, Kangwon National University, Samcheok, 25949, Republic of Korea
  • 4 Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia. mark.butlin@mq.edu.au
  • 5 Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia
Sci Rep, 2018 01 26;8(1):1689.
PMID: 29374229 DOI: 10.1038/s41598-018-20117-6

Abstract

Amyloid β (Aβ) deposition is a hallmark of Alzheimer's disease (AD). Vascular modifications, including altered brain endothelial cell function and structural viability of the blood-brain barrier due to vascular pulsatility, are implicated in AD pathology. Pulsatility of phenomena in the cerebral vasculature are often not considered in in vitro models of the blood-brain barrier. We demonstrate, for the first time, that pulsatile stretch of brain vascular endothelial cells modulates amyloid precursor protein (APP) expression and the APP processing enzyme, β-secretase 1, eventuating increased-Aβ generation and secretion. Concurrent modulation of intercellular adhesion molecule 1 and endothelial nitric oxide synthase (eNOS) signaling (expression and phosphorylation of eNOS) in response to pulsatile stretch indicates parallel activation of endothelial inflammatory pathways. These findings mechanistically support vascular pulsatility contributing towards cerebral Aβ levels.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.