title: Dissecting the pathological effects of human Abeta40 and Abeta42 in Drosophila: a potential model for Alzheimer's disease.
abstract: Accumulation of amyloid-beta (Abeta) peptides in the brain has been suggested to be the primary event in sequential progression of Alzheimer's disease (AD). Here, we use Drosophila to examine whether expression of either the human Abeta40 or Abeta42 peptide in the Drosophila brain can induce pathological phenotypes resembling AD. The expression of Abeta42 led to the formation of diffused amyloid deposits, age-dependent learning defects, and extensive neurodegeneration. In contrast, expression of Abeta40 caused only age-dependent learning defects but did not lead to the formation of amyloid deposits or neurodegeneration. These results strongly suggest that accumulation of Abeta42 in the brain is sufficient to cause behavioral deficits and neurodegeneration. Moreover, Drosophila may serve as a model for facilitating the understanding of molecular mechanisms underlying Abeta toxicity and the discovery of novel therapeutic targets for AD.
authors.affiliation: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
authors.forename: Koichi
authors.initials: K
authors.lastname: Iijima
authors.forename: Hsin-Ping
authors.initials: HP
authors.lastname: Liu
authors.forename: Ann-Shyn
authors.initials: AS
authors.lastname: Chiang
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Hearn
authors.forename: Mary
authors.initials: M
authors.lastname: Konsolaki
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhong
mesh_terms: D000375:Aging / Q000473:pathology; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004330:Drosophila / Q000235:genetics*; D006801:Humans; D013058:Mass Spectrometry; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)