Intravenous Anesthetic Diazepam Does Not Induce Amyloid-β Peptide Oligomerization but Diazepam Co-administered with Halothane Oligomerizes Amyloid-β Peptide: An NMR Study

Amyloid-beta peptide (Abeta) oligomerization has a profound role in Alzheimer's disease pathophysiology. Biophysical studies have shown that smaller sized inhaled anesthetics promote oligomerization by inducing perturbation of three critical amino acid residues (G29, A30, and I31) located in the helix-loop-helix domain of Abeta. In this present experimental study, using state-of-the-art nuclear magnetic resonance, we have monitored the influence of a larger sized intravenous anesthetic, diazepam, as well as diazepam co-dministered with halothane, on Abeta. It was concluded that diazepam (in isolation) does not interact with the G29, A30, and I31 residues, and no Abeta oligomerization occurs in the presence of 0.101 mM diazepam, even after 63 days. However, when diazepam was co-administered with halothane, profound Abeta oligomerization is observed. These results strengthen the hypothesis that the presence of smaller molecular sized anesthetic is instrumental in promoting Abeta oligomerization even when co-administered with a larger sized anesthetic, namely diazepam.