Statins Inhibit Fibrillary [Beta]-Amyloid Induced Inflammation in a Model of the Human Blood Brain Barrier

• Published in: PloS one 2016-06, Vol.11 (6)
• Main Authors: Griffin, Jarred M, Kho, Dan, Graham, E Scott, Nicholson, Louise FB, O'Carroll, Simon J
• Format: Article
• Language: English
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0157483

Background Astrocytes and cerebral endothelial cells are important components of the blood-brain barrier (BBB). Disruption to this barrier through inflammation is a major contributor to Alzheimer's disease (AD) pathology. The amyloid beta (A[Beta]) protein is known to exist in several forms and is a key modulator of AD that is known to cause inflammation and changes to BBB function. While one of these forms, fibrillary A[Beta] (fA[Beta]), is known to cause endothelial cell death at the BBB, no studies have looked specifically at its role on inflammation in a model of the human BBB. Aims To determine if fA[Beta] is inflammatory to the human BBB. As statins have been shown to be anti-inflammatory and protective in AD, we also tested if these could inhibit the inflammatory effect of fA[Beta]. Methods Using cultured cerebral endothelial cells and astrocytes we determined changes in cytokine release, cell toxicity and barrier function in response to fibrillary [Beta]-amyloid1-42 (fA[Beta]1-42) alone and in combination with statins. Results fA[Beta]1-42 induced inflammatory cytokine release from endothelial cells in the absence of cell toxicity. It also induced astrocyte cytokine release and cell death and caused a loss of barrier integrity. Statin treatment inhibited all of these effects. Conclusions We conclude that fA[Beta]1-42 has both inflammatory and cytotoxic effects on the BBB and the protective effect of statins in AD may in part be through inhibiting these effects.