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.

Marungruang, N.Lund University,Lunds universitet,Centrum för preventiv livsmedelsforskning,Universitetets särskilda verksamheter,Food for Health Science Centre,University Specialised Centres(Swepub:lu)appl-nym (author)
Duthilleul, N.Swiss Federal Institute of Technology (author)
Cheatham, V.Swiss Federal Institute of Technology (author)
Mc Coy, K. D.University of Bern (author)
Frisoni, G. B.Geneva University Hospital,University of Geneva (author)
Neher, J. J.University of Tübingen,German Center for Neurodegenerative Diseases (DZNE), Bonn (author)
Fåk, F.Lund University,Lunds universitet,Centrum för preventiv livsmedelsforskning,Universitetets särskilda verksamheter,Food for Health Science Centre,University Specialised Centres(Swepub:lu)cob-ffa (author)
Jucker, MathiasUniversity of Tübingen,German Center for Neurodegenerative Diseases (DZNE), Bonn (author)
Lasser, TheoSwiss Federal Institute of Technology (author)
Bolmont, T.Swiss Federal Institute of Technology,Stemedica International (author)
Swiss Federal Institute of TechnologyCentrum för preventiv livsmedelsforskning (creator_code:org_t)

By the author/editor: Harach, T.; Marungruang, N.; Duthilleul, N.; Cheatham, V.; Mc Coy, K. D.; Frisoni, G. B.; show more...; Neher, J. J.; Fåk, F.; Jucker, Mathias; Lasser, Theo; Bolmont, T.; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

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