title: Chronic nicotine treatment reduces beta-amyloidosis in the brain of a mouse model of Alzheimer's disease (APPsw).
abstract: Alzheimer's disease neuropathology is characterised by beta-amyloid plaques and neurofibrillary tangles. Inhibition of beta-amyloid accumulation may be essential for effective therapy in Alzheimer's disease. In this study we have treated transgenic mice carrying the Swedish mutation of human amyloid precursor protein [Tg(Hu.APP695.K670N-M671L)2576], which develop brain beta-amyloid deposits, with nicotine in drinking fluid (200 microg/mL) from 9-14.5 months of age (5.5 months). A significant reduction in amyloid beta peptide 1-42 positive plaques by more than 80% (p < 0.03) was observed in the brains of nicotine treated compared to sucrose treated transgenic mice. In addition, there was a selective reduction in extractable amyloid beta peptides in nicotine treated mice; cortical insoluble 1-40 and 1-42 peptide levels were lower by 48 and 60%, respectively (p < 0.005), whilst there was no significant change in soluble 1-40 or 1-42 levels. The expression of glial fibrillary acidic protein was not affected by nicotine treatment. These results indicate that nicotine may effectively reduce amyloid beta peptide aggregation in brain and that nicotinic drug treatment may be a novel protective therapy in Alzheimer's disease.
authors.affiliation: Karolinska Institutet, NEUROTEC, Division of Molecular Neuropharmacology, Huddinge University Hospital, Stockholm, Sweden. agneta.nordberg@neurotec.ki.se
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
authors.forename: Ewa
authors.initials: E
authors.lastname: Hellström-Lindahl
authors.forename: Mandy
authors.initials: M
authors.lastname: Lee
authors.forename: Mary
authors.initials: M
authors.lastname: Johnson
authors.forename: Malahat
authors.initials: M
authors.lastname: Mousavi
authors.forename: Ros
authors.initials: R
authors.lastname: Hall
authors.forename: Elaine
authors.initials: E
authors.lastname: Perry
authors.forename: Ivan
authors.initials: I
authors.lastname: Bednar
authors.forename: Jennifer
authors.initials: J
authors.lastname: Court
mesh_terms: D000284:Administration, Oral; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000096:biosynthesis; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry; D002452:Cell Count; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006624:Hippocampus / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009538:Nicotine / Q000008:administration & dosage*; D009833:Olfactory Pathways / Q000737:chemistry; D010446:Peptide Fragments / Q000032:analysis / Q000096:biosynthesis; D058225:Plaque, Amyloid / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D016229:Amyloid beta-Peptides; D005904:Glial Fibrillary Acidic Protein; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D009538:Nicotine