title: Extracellular amyloid formation and associated pathology in neural grafts.
abstract: Amyloid precursor protein (APP) processing and the generation of beta-amyloid peptide (Abeta) are important in the pathogenesis of Alzheimer's disease. Although this has been studied extensively at the molecular and cellular levels, much less is known about the mechanisms of amyloid accumulation in vivo. We transplanted transgenic APP23 and wild-type B6 embryonic neural cells into the neocortex and hippocampus of both B6 and APP23 mice. APP23 grafts into wild-type hosts did not develop amyloid deposits up to 20 months after grafting. In contrast, both transgenic and wild-type grafts into young transgenic hosts developed amyloid plaques as early as 3 months after grafting. Although largely diffuse in nature, some of the amyloid deposits in wild-type grafts were congophilic and were surrounded by neuritic changes and gliosis, similar to the amyloid-associated pathology previously described in APP23 mice. Our results indicate that diffusion of soluble Abeta in the extracellular space is involved in the spread of Abeta pathology, and that extracellular amyloid formation can lead to neurodegeneration.
authors.affiliation: Department of Neuropathology, Institute of Pathology, University of Basel, Schönbeinstrasse 40, CH-4003 Basel, Switzerland.
authors.forename: Melanie
authors.initials: M
authors.lastname: Meyer-Luehmann
authors.forename: Martina
authors.initials: M
authors.lastname: Stalder
authors.forename: Martin C
authors.initials: MC
authors.lastname: Herzig
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Kaeser
authors.forename: Esther
authors.initials: E
authors.lastname: Kohler
authors.forename: Michelle
authors.initials: M
authors.lastname: Pfeifer
authors.forename: Sonia
authors.initials: S
authors.lastname: Boncristiano
authors.forename: Paul M
authors.initials: PM
authors.lastname: Mathews
authors.forename: Marc
authors.initials: M
authors.lastname: Mercken
authors.forename: Dorothee
authors.initials: D
authors.lastname: Abramowski
authors.forename: Matthias
authors.initials: M
authors.lastname: Staufenbiel
authors.forename: Mathias
authors.initials: M
authors.lastname: Jucker
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016380:Brain Tissue Transplantation; D004058:Diffusion; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000235:genetics / Q000378:metabolism*; D005911:Gliosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006085:Graft Survival / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology / Q000637:transplantation; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport / Q000235:genetics; D011930:Reaction Time / Q000235:genetics; D012995:Solubility; D015854:Up-Regulation / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor