Amyloid Beta 25–35 induces blood-brain barrier disruption in vitro

Elvis Cuevas, Hector Rosas-Hernandez, Susan M. Burks, Manuel A. Ramirez-Lee, Aida Guzman, Syed Z. Imam, Syed F. Ali, Sumit Sarkar

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

The amyloid β-peptide (Aβ) is transported across the blood-brain barrier (BBB) by binding with the receptor for advanced glycation end products (RAGE). Previously, we demonstrated that the Aβ fraction 25–35 (Aβ25–35) increases RAGE expression in the rat hippocampus, likely contributing to its neurotoxic effects. However, it is still debated if the interaction of Aβ with RAGE compromises the BBB function in Alzheimer’ disease (AD). Here, we evaluated the effects of Aβ25–35 in an established in vitro model of the BBB. Rat brain microvascular endothelial cells (rBMVECs) were treated with 20 μM active Aβ25–35 or the inactive Aβ35–25 (control), for 24 h. Exposure to Aβ25–35 significantly decreased cell viability, increased cellular necrosis, and increased the production of reactive oxygen species (ROS), which triggered a decrease in the enzyme glutathione peroxidase when compared to the control condition. Aβ25–35 also increased BBB permeability by altering the expression of tight junction proteins (decreasing zonula occludens-1 and increasing occludin). Aβ25–35 induced monolayer disruption and cellular disarrangement of the BBB, with RAGE being highly expressed in the zones of disarrangement. Together, these data suggest that Aβ25–35-induces toxicity by compromising the functionality and integrity of the BBB in vitro. [Figure not available: see fulltext.].

Original languageEnglish (US)
Pages (from-to)1365-1374
Number of pages10
JournalMetabolic brain disease
Volume34
Issue number5
DOIs
StatePublished - Oct 1 2019
Externally publishedYes

Keywords

  • Amyloid β fraction 25–35
  • Blood-brain barrier
  • Oxidative stress
  • Permeability
  • RAGE
  • Zonula occludens 1

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Fingerprint

Dive into the research topics of 'Amyloid Beta 25–35 induces blood-brain barrier disruption in vitro'. Together they form a unique fingerprint.

Cite this