Nicotine reduces Aβ in the brain and cerebral vessels of APPsw mice

Ten days treatment with nicotine reduced insoluble amyloid Abeta1-40 and Abeta1-42 peptides by 80% in the cortex of 9-month-old APPsw mice, which is more than that observed in 14.5-month-old mice following nicotine treatment for 5.5 months. A reduction in Abeta associated with cerebral vessels was observed in addition to that deposited as parenchymal plaques after 5.5 months treatment. The diminution in Abeta peptides observed was not accompanied by changes in brain alpha, beta or gamma secretase-like activities, NGF or BDNF protein expression measured in brain homogenates. A significant increase in sAPP was observed after nicotine treatment of SH-SY5Yneuroblastoma cells that could be blocked by the nicotinic antagonist mecamylamine. Attenuation of elevated [I-125]-alphabungarotoxin binding (alpha7) in APPsw mice was observed after 5.5 months nicotine treatment. Both these observations suggest that the reduction in insoluble Abeta by nicotine might be in part mediated via the alpha7 nicotinic receptor. Further studies are required to identify potential mechanisms of the nicotine's amyloid-reducing effect.