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

The amyloid beta-peptide (A beta) is transported across the blood-brain barrier (BBB) by binding with the receptor for advanced glycation end products (RAGE). Previously, we demonstrated that the A beta fraction 25-35 (A beta(25-35)) increases RAGE expression in the rat hippocampus, likely contributing to its neurotoxic effects. However, it is still debated if the interaction of A beta with RAGE compromises the BBB function in Alzheimer' disease (AD). Here, we evaluated the effects of A beta(25-35) in an established in vitro model of the BBB. Rat brain microvascular endothelial cells (rBMVECs) were treated with 20 mu M active A beta(25-35) or the inactive A beta(35-25) (control), for 24 h. Exposure to A beta(25-35) 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. A beta(25-35) also increased BBB permeability by altering the expression of tight junction proteins (decreasing zonula occludens-1 and increasing occludin). A beta(25-35) induced monolayer disruption and cellular disarrangement of the BBB, with RAGE being highly expressed in the zones of disarrangement. Together, these data suggest that A beta(25-35)-induces toxicity by compromising the functionality and integrity of the BBB in vitro.