Isoflurane and desflurane at clinically relevant concentrations induce amyloid beta-peptide oligomerization: an NMR study

Abstract

Current understanding on Alzheimer's disease (AD) reveals that soluble amyloid beta-peptide (Abeta) oligomeric formation plays an important role in AD pathophysiology. A potential role for several inhaled anesthetics in promoting Abeta oligomer formation has been suggested. Using a nuclear magnetic resonance (NMR) study, we previously demonstrated that at a high concentration (higher than clinically relevant concentrations), the inhaled anesthetics halothane and isoflurane, interact with specific amino acid residues (G29, A30, and I31) and induce Abeta oligomerization. The present study confirms this is true at a clinically relevant concentration. Isoflurane and desflurane induce Abeta oligomerization by inducing chemical shift changes of the critical amino acid residues (G29, A30, and I31), reinforcing the evidence that perturbation of these three crucial residues indeed plays an important role in oligomerization. These findings support the emerging hypothesis that several commonly used inhaled anesthetics could be involved in neurodegeneration, as well as risk factor for accelerating the onset of AD.