Amyloid Beta-Derived Diffusible Ligands (ADDLs) Induce Abnormal Expression of Insulin Receptors in Rat Hippocampal Neurons

Amyloid beta (A beta) is an important pathogenic factor in Alzheimer's disease (AD). In this study, we investigated the hypothesis that administration of amyloid-derived diffusible ligands (ADDLs) prepared from a synthetic A beta (1-42) amyloid peptide can cause defective expression of insulin receptors (IRs). To this end, primary rat hippocampal neurons were treated with various concentrations of ADDLs and expression levels of IRs were measured using real-time PCR and western blots. In these experiments, the expression of IRs significantly increased following treatment with low concentrations of A beta (1-42). In contrast, when higher concentrations of A beta (1-42) were applied, the number of apoptotic cells present increased, and expression of IRs significantly decreased. In combination, these results suggest that ADDLs is able to induce abnormal expression of IRs and interrupt normal insulin signaling, thereby potentially contributing to central insulin resistance that can occur during progression of AD.