title: Fimbria-fornix lesion does not affect APP levels and amyloid deposition in the hippocampus of APP+PS1 double transgenic mice.
abstract: The deposition of amyloid beta peptides (Abeta) and cholinergic dysfunction are two characteristic features of Alzheimer's disease. Several studies have suggested that a compromised cholinergic transmission can increase the amount of amyloid precursor protein (APP) in the denervated cortex (or hippocampus); however, whether this will increase Abeta production is unknown. To investigate the relation between cholinergic neurotransmission and APP metabolism, and the possible role of cholinergic dysfunction in the development of amyloid neuropathology, we lesioned the fimbria-fornix pathway in APP+PS1 double transgenic mice, at 5 and 7 months of age. Three months and 11 months postlesion, the mice were sacrificed for biochemical and histopathological analyses. The fimbria-fornix transection resulted in a substantial depletion of cholinergic markers in the hippocampus at both time points. Three months postlesion, hippocampal APP and Abeta levels were not significantly changed. At 11 months postlesion, the fimbria-fornix lesion did not result in an alteration in either the hippocampal Abeta levels or the extent of Abeta deposition, as assessed by amyloid plaque counts and image analysis of Abeta load in the 18-month-old APP+PS1 mice. Our findings indicate that APP metabolism in mice may be dissociated from cholinergic neurotransmission rather than related as previously suggested in other mammalian species.
authors.affiliation: Department of Neuroscience and Neurology, University of Kuopio, FIN 70211, Kuopio, Finland. liu.li@uku.fi
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Sami
authors.initials: S
authors.lastname: Ikonen
authors.forename: Tero
authors.initials: T
authors.lastname: Tapiola
authors.forename: Heikki
authors.initials: H
authors.lastname: Tanila
authors.forename: Thomas
authors.initials: T
authors.lastname: van Groen
mesh_terms: D000110:Acetylcholinesterase / Q000096:biosynthesis; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000096:biosynthesis; D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000032:analysis / Q000096:biosynthesis; D004195:Disease Models, Animal; D020712:Fornix, Brain / Q000503:physiopathology* / Q000601:surgery; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000503:physiopathology / Q000601:surgery; D019635:Neurosurgical Procedures; D010446:Peptide Fragments / Q000032:analysis / Q000096:biosynthesis
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase