Progression of Seed-Induced Aβ Deposition within the Limbic Connectome.

Autor:	Ye L; 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., Hamaguchi T; Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany., Fritschi SK; 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., Eisele YS; Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany., Obermüller U; Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany., Jucker M; Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany., Walker LC; 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.
Jazyk:	angličtina
Zdroj:	Brain pathology (Zurich, Switzerland) [Brain Pathol] 2015 Nov; Vol. 25 (6), pp. 743-52. Date of Electronic Publication: 2015 Mar 24.
DOI:	10.1111/bpa.12252
Abstrakt:	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. (© 2015 International Society of Neuropathology.)
Databáze:	MEDLINE
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