Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota.
Alzheimer's disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer's disease is not known. To this end we sequenced bacterial 16S rRNA from fecal samples of Aβ precursor protein (APP) transgenic mouse model and found a remarkable shift in the gut microbiota as compared to non-transgenic wild-type mice. Subsequently we generated germ-free APP transgenic mice and found a drastic reduction of cerebral Aβ amyloid pathology when compared to control mice with intestinal microbiota. Importantly, colonization of germ-free APP transgenic mice with microbiota from conventionally-raised APP transgenic mice increased cerebral Aβ pathology, while colonization with microbiota from wild-type mice was less effective in increasing cerebral Aβ levels. Our results indicate a microbial involvement in the development of Abeta amyloid pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases.
Laboratoire d'Optique biomédicale, Institute of Microengineering, School of Engineering, Ecole Polytechnique Fédérale de Lausanne, CH1015 Lausanne, Switzerland.
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Harach
Food for Health Science Centre, Lund University, Medicon Village, 22381 Lund, Sweden.
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Marungruang
Laboratoire d'Optique biomédicale, Institute of Microengineering, School of Engineering, Ecole Polytechnique Fédérale de Lausanne, CH1015 Lausanne, Switzerland.
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Duthilleul
Laboratoire d'Optique biomédicale, Institute of Microengineering, School of Engineering, Ecole Polytechnique Fédérale de Lausanne, CH1015 Lausanne, Switzerland.
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Cheatham
Mucosal Immunology Lab, Department of Clinical Research, University of Bern, Murtenstrasse, 35 CH - 3010 Bern, Switzerland.
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Mc Coy
Memory Clinic and LANVIE - Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland.
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Frisoni
German Centre for Neurodegenerative Diseases (DZNE), Tübingen, D-72076 Tübingen, Germany.|Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany.
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Neher
Food for Health Science Centre, Lund University, Medicon Village, 22381 Lund, Sweden.
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Fåk
German Centre for Neurodegenerative Diseases (DZNE), Tübingen, D-72076 Tübingen, Germany.|Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany.
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Jucker
Laboratoire d'Optique biomédicale, Institute of Microengineering, School of Engineering, Ecole Polytechnique Fédérale de Lausanne, CH1015 Lausanne, Switzerland.
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Lasser
Laboratoire d'Optique biomédicale, Institute of Microengineering, School of Engineering, Ecole Polytechnique Fédérale de Lausanne, CH1015 Lausanne, Switzerland.|Stemedica International, Avenue de Sévelin 20, CH1004 Lausanne, Switzerland.
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Bolmont