title: Abeta42 is essential for parenchymal and vascular amyloid deposition in mice.
abstract: Considerable circumstantial evidence suggests that Abeta42 is the initiating molecule in Alzheimer's disease (AD) pathogenesis. However, the absolute requirement for Abeta42 for amyloid deposition has never been demonstrated in vivo. We have addressed this by developing transgenic models that express Abeta1-40 or Abeta1-42 in the absence of human amyloid beta protein precursor (APP) overexpression. Mice expressing high levels of Abeta1-40 do not develop overt amyloid pathology. In contrast, mice expressing lower levels of Abeta1-42 accumulate insoluble Abeta1-42 and develop compact amyloid plaques, congophilic amyloid angiopathy (CAA), and diffuse Abeta deposits. When mice expressing Abeta1-42 are crossed with mutant APP (Tg2576) mice, there is also a massive increase in amyloid deposition. These data establish that Abeta1-42 is essential for amyloid deposition in the parenchyma and also in vessels.
authors.affiliation: Department Neuroscience Mayo Clinic College of Medicine Jacksonville, Florida 32224.
authors.forename: Eileen
authors.initials: E
authors.lastname: McGowan
authors.affiliation: Department Neuroscience Mayo Clinic College of Medicine Jacksonville, Florida 32224.
authors.forename: Fiona
authors.initials: F
authors.lastname: Pickford
authors.affiliation: Department Neuroscience Mayo Clinic College of Medicine Jacksonville, Florida 32224.
authors.forename: Jungsu
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department Neuroscience Mayo Clinic College of Medicine Jacksonville, Florida 32224.
authors.forename: Luisa
authors.initials: L
authors.lastname: Onstead
authors.affiliation: Department Neuroscience Mayo Clinic College of Medicine Jacksonville, Florida 32224.
authors.forename: Jason
authors.initials: J
authors.lastname: Eriksen
authors.affiliation: Department Neuroscience Mayo Clinic College of Medicine Jacksonville, Florida 32224.
authors.forename: Cindy
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department Neuroscience Mayo Clinic College of Medicine Jacksonville, Florida 32224.
authors.forename: Lisa
authors.initials: L
authors.lastname: Skipper
authors.affiliation: Department Neuroscience Mayo Clinic College of Medicine Jacksonville, Florida 32224.
authors.forename: M Paul
authors.initials: MP
authors.lastname: Murphy
authors.affiliation: Department Neuroscience Mayo Clinic College of Medicine Jacksonville, Florida 32224.
authors.forename: Jenny
authors.initials: J
authors.lastname: Beard
authors.affiliation: Department Neuroscience Mayo Clinic College of Medicine Jacksonville, Florida 32224.
authors.forename: Pritam
authors.initials: P
authors.lastname: Das
authors.affiliation: Department Neuroscience Mayo Clinic College of Medicine Jacksonville, Florida 32224.
authors.forename: Karen
authors.initials: K
authors.lastname: Jansen
authors.affiliation: Department Neuroscience Mayo Clinic College of Medicine Jacksonville, Florida 32224.
authors.forename: Michael
authors.initials: M
authors.lastname: DeLucia
authors.affiliation: Department Neuroscience Mayo Clinic College of Medicine Jacksonville, Florida 32224.
authors.forename: Wen-Lang
authors.initials: WL
authors.lastname: Lin
authors.affiliation: Department of Human Genetics Mount Sinai School of Medicine New York, New York 10029.
authors.forename: Georgia
authors.initials: G
authors.lastname: Dolios
authors.affiliation: Department of Human Genetics Mount Sinai School of Medicine New York, New York 10029.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department Neuroscience Mayo Clinic College of Medicine Jacksonville, Florida 32224.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Eckman
authors.affiliation: Department Neuroscience Mayo Clinic College of Medicine Jacksonville, Florida 32224.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.affiliation: Department Neuroscience Mayo Clinic College of Medicine Jacksonville, Florida 32224.
authors.forename: Mike
authors.initials: M
authors.lastname: Hutton
authors.affiliation: Laboratory of Neurogenetics National Institute on Aging National Institutes of Health Bethesda, Maryland 20892.
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.affiliation: Department Neuroscience Mayo Clinic College of Medicine Jacksonville, Florida 32224.
authors.forename: Todd
authors.initials: T
authors.lastname: Golde
mesh_terms: D000367:Age Factors; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D052160:Benzothiazoles; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D016657:Cerebral Amyloid Angiopathy / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009154:Mutation; D010446:Peptide Fragments / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D010841:Pia Mater / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D013844:Thiazoles / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D052160:Benzothiazoles; D005904:Glial Fibrillary Acidic Protein; D010446:Peptide Fragments; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C009462:thioflavin T