Nicotine breaks down preformed Alzheimer's beta-amyloid fibrils in vitro.
BACKGROUND
Cerebral deposition of amyloid beta-peptide (Abeta) 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 Abeta toxicity via the upregulation of nicotinic receptors, as well as via the inhibition of beta-amyloid fibril (fAbeta) formation from Abeta.


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 fAbeta(1-40) and fAbeta(1-42) at pH 7.5 at 37 degrees C in vitro.


RESULTS
Nicotine dose-dependently inhibited fAbeta(1-40) and fAbeta(1-42) formation from fresh Abeta(1-40) and Abeta(1-42), respectively, as well as the extension reaction of both fAbetas. Moreover, nicotine disrupted preformed fAbeta(1-40) and fAbeta(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 fAbeta formation but also by the disruption of preformed fAbeta. Additionally, this effect may be attributed to N-methylpyrrolidine moieties of nicotine.
Ono
Kenjiro
K
Department of Pathology, Fukui Medical University, Fukui, Japan.
Hasegawa
Kazuhiro
K
Yamada
Masahito
M
Naiki
Hironobu
H
D000544:Alzheimer Disease / Q000378:metabolism* / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000378:metabolism; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008859:Microscopy, Polarization; D016874:Neurofibrillary Tangles / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology* / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D013050:Spectrometry, Fluorescence
D016229:Amyloid beta-Peptides; D011725:Pyridines; D011759:Pyrrolidines; C054965:N-methylpyrrolidine; D009538:Nicotine; C023666:pyridine