Nicotine breaks down preformed Alzheimer’s β-amyloid fibrils in vitro

Background Cerebral deposition of amyloid β-peptide (Aβ) is a major neuropathologic feature in Alzheimer’s disease (AD). A consistent protective effect of smoking on AD has been documented by many case-control studies. It has been suggested that nicotine, a major component of cigarette smoke, protects neurons against Aβ toxicity via the upregulation of nicotinic receptors, as well as via the inhibition of β-amyloid fibril (fAβ) formation from Aβ. Methods We used fluorescence spectroscopy with thioflavin T and electron microscopy to examine the effects of nicotine, pyridine, and N-methylpyrrolidine on the formation, extension, and disruption of fAβ(1-40) and fAβ(1-42) at pH 7.5 at 37°C in vitro. Results Nicotine dose-dependently inhibited fAβ(1-40) and fAβ(1-42) formation from fresh Aβ(1-40) and Aβ(1-42), respectively, as well as the extension reaction of both fAβs. Moreover, nicotine disrupted preformed fAβ(1-40) and fAβ(1-42). These effects of nicotine were observed at concentrations above 10 mmol/L and were similar to those of N-methylpyrrolidine. Conclusions The antiamyloidogenic effect of nicotine may be exerted not only by the inhibition of fAβ formation but also by the disruption of preformed fAβ. Additionally, this effect may be attributed to N-methylpyrrolidine moieties of nicotine