title: Chronic elevation of amyloid precursor protein in the neocortex or hippocampus of marmosets with selective cholinergic lesions.
abstract: In vitro studies have consistently demonstrated a link between cholinergic neurotransmission and amyloid precursor protein metabolism, although few studies have examined such a relationship in vivo and none have been conducted in primate species. The purpose of this study was to test the hypothesis that a reduction in cholinergic activity in neocortical and hippocampal areas consequent upon destruction of ascending cholinergic projections may lead to long-term changes in levels of amyloid precursor protein in these target areas in a primate species. The status of three synaptic proteins associated with neurotransmitter release, synaptophysin, syntaxin and SNAP-25, was also been examined. Selective immunolesions of the basal forebrain cholinergic projections led to increases in amyloid precursor protein-like immunoreactivity in hippocampus and cortex, measured 8 months postlesion. Furthermore, reductions in cortical and hippocampal SNAP-25, but not syntaxin or synaptophysin, immunoreactivity were observed. These results imply that the reduced cholinergic activity characteristic of Alzheimer's disease may contribute to the continuing emergence of neuropathology in addition to the well-known association with cognitive dysfunction.
authors.affiliation: Dementia Research Laboratory, Neuroscience Research Centre, GKT School of Biomedical Sciences, King's College London, United Kingdom.
authors.forename: M J
authors.initials: MJ
authors.lastname: Ramirez
authors.forename: R M
authors.initials: RM
authors.lastname: Ridley
authors.forename: H F
authors.initials: HF
authors.lastname: Baker
authors.forename: C J
authors.initials: CJ
authors.lastname: Maclean
authors.forename: W G
authors.initials: WG
authors.lastname: Honer
authors.forename: P T
authors.initials: PT
authors.lastname: Francis
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D002144:Callithrix; D002799:Cholinergic Fibers / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D019579:Neocortex / Q000737:chemistry / Q000378:metabolism*; D013194:Staining and Labeling
chemical_list: D016564:Amyloid beta-Protein Precursor