Amyloid- beta peptide increases cell surface localization of alpha 7 ACh receptor to protect neurons from amyloid beta -induced damage

Amyloid- beta peptide 1-42 (A beta 1-42) reduced PC-12 cell viability in a concentration (1-10 mu M)- and treatment time (48-72 h)-dependent manner. Nicotine prevented A beta 1-42-induced PC-12 cell death, but conversely, the alpha 7 ACh receptor antagonist alpha -bungarotoxin enhanced A beta 1-42-induced cell toxicity. Extracellularly applied A beta 1-42 significantly increased cell surface localization of alpha 7 ACh receptor in PC-12 cells as compared with that for non-treated control cells. Cell surface localization of alpha 7 ACh receptor in the brain of 5xFAD mouse, an animal model of Alzheimer's disease (AD), apparently increased in an age (1-12 months)-dependent manner in association with increased accumulation of A beta 1-42 in the plasma membrane component. Taken together, these results indicate that A beta 1-42 promotes translocation of alpha 7 ACh receptor towards the cell surface and that alpha 7 ACh receptor rescues neuronal cells from A beta 1-42-induced damage.