title: Murine Aβ over-production produces diffuse and compact Alzheimer-type amyloid deposits.
abstract: BACKGROUND
  Transgenic overexpression of amyloid precursor protein (APP) genes that are either entirely human in sequence or have humanized Aβ sequences can produce Alzheimer-type amyloidosis in mice, provided the transgenes also encode mutations linked to familial Alzheimer's Disease (FAD). Although transgenic mice have been produced that overexpress wild-type mouse APP, no mice have been generated that express mouse APP with FAD mutations. Here we describe two different versions of such mice that produce amyloid deposits consisting of entirely of mouse Aβ peptides. One line of mice co-expresses mouse APP-Swedish (moAPPswe) with a human presenilin exon-9 deleted variant (PS1dE9) and another line expresses mouse APP-Swedish/Indiana (APPsi) using tetracycline-regulated vectors (tet.moAPPsi).
  
  
  RESULTS
  Both lines of mice that produce mouse Aβ develop amyloid deposits, with the moAPPswe/PS1dE9 mice developing extracellular compact, cored, neuritic deposits that primarily localize to white matter tracts and meningial layers, whereas the tet.moAPPsi mice developed extracellular diffuse cortical/hippocampal deposits distributed throughout the parenchyma.
  
  
  CONCLUSIONS
  These findings demonstrate that murine Aβ peptides have the capacity to produce amyloid deposits that are morphologically similar to deposits found in human AD provided the murine APP gene harbors mutations linked to human FAD.
authors.affiliation: Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA.|McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA.|SantaFe HealthCare Alzheimer's Disease Research Center, University of Florida, Gainesville, FL, 32610, USA.|Department of Neuroscience, University of Florida, 1275 Center Dr., Box 100159, Gainesville, FL, 32610, USA.
authors.forename: Guilian
authors.initials: G
authors.lastname: Xu
authors.affiliation: Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA.|Department of Neuroscience, University of Florida, 1275 Center Dr., Box 100159, Gainesville, FL, 32610, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ran
authors.affiliation: Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA.|SantaFe HealthCare Alzheimer's Disease Research Center, University of Florida, Gainesville, FL, 32610, USA.|Department of Neuroscience, University of Florida, 1275 Center Dr., Box 100159, Gainesville, FL, 32610, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Fromholt
authors.affiliation: Department of Medicine, University of Florida, Gainesville, FL, 32610, USA.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Fu
authors.affiliation: Department of Pathology, University of Florida College of Medicine, University of Florida, Gainesville, FL, 32610, USA.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Yachnis
authors.affiliation: Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA.|McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA.|Department of Neuroscience, University of Florida, 1275 Center Dr., Box 100159, Gainesville, FL, 32610, USA.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Golde
authors.affiliation: Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA. drb1@ufl.edu.|McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA. drb1@ufl.edu.|SantaFe HealthCare Alzheimer's Disease Research Center, University of Florida, Gainesville, FL, 32610, USA. drb1@ufl.edu.|Department of Neuroscience, University of Florida, 1275 Center Dr., Box 100159, Gainesville, FL, 32610, USA. drb1@ufl.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Borchelt
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009447:Neuroblastoma / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism*; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D005904:Glial Fibrillary Acidic Protein; D053764:Presenilin-1; D049452:Green Fluorescent Proteins