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

Harach, T.; Marungruang, N. LU ; Duthilleul, N.; Cheatham, V.; Mc Coy, K. D.; Frisoni, G. B.; Neher, J. J.; Fåk, F. LU ; Jucker, Mathias and Lasser, Theo, et al. (2017) In Scientific Reports 7.
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... (More)

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.

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published
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Scientific Reports
volume
7
publisher
Nature Publishing Group
external identifiers
  • scopus:85011954434
  • wos:000393636100001
ISSN
2045-2322
DOI
10.1038/srep41802
language
English
LU publication?
yes
id
11e94b1d-0994-4543-980a-805429c583af
date added to LUP
2017-02-23 07:58:14
date last changed
2018-03-11 04:37:50
@article{11e94b1d-0994-4543-980a-805429c583af,
  abstract     = {<p>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.</p>},
  articleno    = {41802},
  author       = {Harach, T. and Marungruang, N. and Duthilleul, N. and Cheatham, V. and Mc Coy, K. D. and Frisoni, G. B. and Neher, J. J. and Fåk, F. and Jucker, Mathias and Lasser, Theo and Bolmont, T.},
  issn         = {2045-2322},
  language     = {eng},
  month        = {02},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota},
  url          = {http://dx.doi.org/10.1038/srep41802},
  volume       = {7},
  year         = {2017},
}