title: Progression of Seed-Induced Aβ Deposition within the Limbic Connectome.
abstract: An important early event in the pathogenesis of Alzheimer's disease (AD) is the aberrant polymerization and extracellular accumulation of amyloid-β peptide (Aβ). In young transgenic mice expressing the human Aβ-precursor protein (APP), deposits of Aβ can be induced by the inoculation of minute amounts of brain extract containing Aβ aggregates ("Aβ seeds"), indicative of a prion-like seeding phenomenon. Moreover, focal intracerebral injection of Aβ seeds can induce deposits not only in the immediate vicinity of the injection site, but, with time, also in distal regions of the brain. However, it remains uncertain whether the spatial progression of Aβ deposits occurs via nonsystematic diffusion from the injection site to proximal regions or via directed transit along neuroanatomical pathways. To address this question, we analyzed the spatiotemporal emergence of Aβ deposits in two different APP-transgenic mouse models that had been previously inoculated with Aβ seeds into the hippocampal formation. The results revealed a specific, neuroanatomically constrained pattern of induced Aβ deposits in structures corresponding to the limbic connectome, supporting the hypothesis that neuronal pathways act as conduits for the movement of proteopathic agents among brain regions, thereby facilitating the progression of disease.
authors: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.|Graduate School of Cellular and Molecular Neuroscience, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors: Lan
authors: L
authors: Ye
authors: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors: Tsuyoshi
authors: T
authors: Hamaguchi
authors: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.|Graduate School of Cellular and Molecular Neuroscience, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors: Sarah K
authors: SK
authors: Fritschi
authors: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors: Yvonne S
authors: YS
authors: Eisele
authors: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors: Ulrike
authors: U
authors: Obermüller
authors: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors: Mathias
authors: M
authors: Jucker
authors: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.|Yerkes National Primate Research Center, Emory University, Atlanta, GA.|Department of Neurology, Emory University, Atlanta, GA.
authors: Lary C
authors: LC
authors: Walker
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D063132:Connectome; D018450:Disease Progression; D006801:Humans; D008032:Limbic System / Q000378:metabolism* / Q000473:pathology*; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor
keywords: Alzheimer; hippocampus; neurodegeneration; prion; transgenic mice