title: Cholinergic deafferentation of the rabbit cortex: a new animal model of Abeta deposition.
abstract: Brain deposition of the amyloid beta-peptide (Abeta) is a critical step in the pathogenesis of Alzheimer's disease (AD) and human cerebral amyloid angiopathy (CAA). A small fraction of AD and CAA cases are caused by gene mutations leading to increased production and deposition of Abeta, but for the majority, there is no known direct genetic cause. We have hypothesized that Abeta deposition in these sporadic cases occurs as a result of cortical cholinergic deafferentation. Here we show that cortical cholinergic deafferentation, induced in rabbits by a selective immunotoxin, leads to Abeta deposition in cerebral blood vessels and perivascular neuropil. Biochemical measurements confirmed that lesioned animals had 2.5- and 8-fold elevations of cortical Abeta40 and Abeta42, respectively. Cholinergic deafferentation may be one factor that can contribute to Abeta deposition.
authors.affiliation: Sun Health Research Institute, Sun City, AZ 85351, USA. tbeach@mail.sunhealth.org
authors.forename: T G
authors.initials: TG
authors.lastname: Beach
authors.forename: P E
authors.initials: PE
authors.lastname: Potter
authors.forename: Y M
authors.initials: YM
authors.lastname: Kuo
authors.forename: M R
authors.initials: MR
authors.lastname: Emmerling
authors.forename: R A
authors.initials: RA
authors.lastname: Durham
authors.forename: S D
authors.initials: SD
authors.lastname: Webster
authors.forename: D G
authors.initials: DG
authors.lastname: Walker
authors.forename: L I
authors.initials: LI
authors.lastname: Sue
authors.forename: S
authors.initials: S
authors.lastname: Scott
authors.forename: K J
authors.initials: KJ
authors.lastname: Layne
authors.forename: A E
authors.initials: AE
authors.lastname: Roher
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016657:Cerebral Amyloid Angiopathy / Q000503:physiopathology; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology*; D002795:Choline O-Acetyltransferase / Q000187:drug effects / Q000378:metabolism; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D003714:Denervation; D004195:Disease Models, Animal; D000922:Immunotoxins / Q000494:pharmacology; D009410:Nerve Degeneration / Q000139:chemically induced*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009498:Neurotoxins / Q000494:pharmacology; D011817:Rabbits
chemical_list: D016229:Amyloid beta-Peptides; D000922:Immunotoxins; D009498:Neurotoxins; D002795:Choline O-Acetyltransferase