Nicotine lowers the secretion of the Alzheimer's amyloid β-protein precursor that contains amyloid β-peptide in rat

摘要: Reports of an inverse relationship between nicotine intake, due to cigarette smoking, and the incidence Alzheimer's disease (AD) prompted us investigate effects on amyloid beta-protein precursor (AbetaPP) processing in rat. Over-production and/or altered metabolism AbetaPP, resulting increased beta-peptide (Abeta), appear pivotal pathogenesis AD. Abeta is generated proteolytically from betaPP by a group secretases. AbetaPP cleavage gamma-secretase results secretion truncated soluble (sAPPgamma) that contains intact Abeta. Nicotine, 1 8 mg/kg/day, doses commensurate with smoking higher but well tolerated dose, respectively, was administered over 14 days Western blot analysis performed sAPP fragments. Both significantly reduced sAPPgamma. These actions were blocked nicotinic receptor antagonism. Whereas antagonists alone had no effect either total or sAPPgammalevels CSF, muscarinic antagonism elevated them; suggesting rather than silence alters favor potentially amyloidogenic route. Combined attenuated action latter elevate sAPPgamma, indicating modifies away products. suggest within brain, levels sAPP, sAPPgamma and, accordingly, are subject cholinergic manipulation, offering therapeutic potential at level decrease Abetadeposition.