Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • T. Harach
  • N. Marungruang
  • N. Duthilleul
  • V. Cheatham
  • K. D. Mc Coy
  • G. B. Frisoni
  • J. J. Neher
  • F. Fåk
  • Mathias Jucker
  • Theo Lasser
  • T. Bolmont
Organisations
External organisations
  • Ecole Polytechnique Federale de Lausanne
  • University of Bern
  • University of Geneva
  • German Center for Neurodegenerative Diseases
  • Geneva University Hospital
  • University of Tübingen
  • Stemedica International
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences
Original languageEnglish
Article number41802
JournalScientific Reports
Volume7
StatePublished - 2017 Feb 8
Peer-reviewedYes