title: Multiple factors contribute to the peripheral induction of cerebral β-amyloidosis.
abstract: Deposition of aggregated amyloid-β (Aβ) peptide in brain is an early event and hallmark pathology of Alzheimer's disease and cerebral Aβ angiopathy. Experimental evidence supports the concept that Aβ multimers can act as seeds and structurally corrupt other Aβ peptides by a self-propagating mechanism. Here we compare the induction of cerebral β-amyloidosis by intraperitoneal applications of Aβ-containing brain extracts in three Aβ-precursor protein (APP) transgenic mouse lines that differ in levels of transgene expression in brain and periphery (APP23 mice, APP23 mice lacking murine APP, and R1.40 mice). Results revealed that beta-amyloidosis induction, which could be blocked with an anti-Aβ antibody, was dependent on the amount of inoculated brain extract and on the level of APP/Aβ expression in the brain but not in the periphery. The induced Aβ deposits in brain occurred in a characteristic pattern consistent with the entry of Aβ seeds at multiple brain locations. Intraperitoneally injected Aβ could be detected in blood monocytes and some peripheral tissues (liver, spleen) up to 30 d after the injection but escaped histological and biochemical detection thereafter. These results suggest that intraperitoneally inoculated Aβ seeds are transported from the periphery to the brain in which corruptive templating of host Aβ occurs at multiple sites, most efficiently in regions with high availability of soluble Aβ.
authors: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany, German Center for Neurodegenerative Diseases, D-72076 Tübingen, Germany, and yvonne.s.eisele@gmail.com mathias.jucker@uni-tuebingen.de.
authors: Yvonne S
authors: YS
authors: Eisele
authors: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany, Graduate School of Cellular and Molecular Neuroscience, University of Tübingen, D-72074 Tübingen, Germany, German Center for Neurodegenerative Diseases, D-72076 Tübingen, Germany, and.
authors: Sarah K
authors: SK
authors: Fritschi
authors: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany.
authors: Tsuyoshi
authors: T
authors: Hamaguchi
authors: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany, German Center for Neurodegenerative Diseases, D-72076 Tübingen, Germany, and.
authors: Ulrike
authors: U
authors: Obermüller
authors: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany, German Center for Neurodegenerative Diseases, D-72076 Tübingen, Germany, and.
authors: Petra
authors: P
authors: Füger
authors: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany, German Center for Neurodegenerative Diseases, D-72076 Tübingen, Germany, and.
authors: Angelos
authors: A
authors: Skodras
authors: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany, German Center for Neurodegenerative Diseases, D-72076 Tübingen, Germany, and.
authors: Claudia
authors: C
authors: Schäfer
authors: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany, German Center for Neurodegenerative Diseases, D-72076 Tübingen, Germany, and.
authors: Jörg
authors: J
authors: Odenthal
authors: Institute for Virology, Technische Universität München/Helmholtz Zentrum München, D-81675 Munich, Germany.
authors: Mathias
authors: M
authors: Heikenwalder
authors: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany, German Center for Neurodegenerative Diseases, D-72076 Tübingen, Germany, and.
authors: Matthias
authors: M
authors: Staufenbiel
authors: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany, German Center for Neurodegenerative Diseases, D-72076 Tübingen, Germany, and yvonne.s.eisele@gmail.com mathias.jucker@uni-tuebingen.de.
authors: Mathias
authors: M
authors: Jucker
mesh_terms: D016229:Amyloid beta-Peptides / Q000276:immunology / Q000378:metabolism* / Q000633:toxicity*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000686:Amyloidosis / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001773:Blood Cells / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010529:Peritoneal Cavity / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies
keywords: Abeta; cerebral beta-amyloidosis; peripheral induction; seeding