Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota
By T. Harach, N. Marungruang, N. Duthilleul, V. Cheatham, K. Coy, Giovanni B. Frisoni, J. Neher, F. Fåk, Mathias Jucker, T. Lasser and 1 more. Scientific Reports, 2017
790 citations recorded by the source corpus.
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.
Subfields: Molecular Biology, Oncology, Physiology
View Paper: https://www.semanticscholar.org/paper/fd6cfc83f74238919690cfff8682610e299be3d3
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Citations in the corpus
- The Gut Microbiota and Alzheimer’s Disease (2017, positive): “…alterations were observed in the gut microbiota composition of conventionally raised 8-month-old APP/PS1 mice compared to wild-type mice, including reduced levels of Firmicutes, Verrucomicrobia, Proteobacteria, Actinobacteria, and a concurrent increase in Bac-teroidetes and Tenericutes [76].”
- Brain-Gut-Microbiota Axis in Alzheimer’s Disease (2019, methodology): “cerebral Aβ pathology, and this increase was less effective when wild type mice microbiota was used.(79) Similarly, germ-free mice overexpressing α-syn, used as a model of PD, developed reduced α-syn inclusions and microglial activation compared to the controls.”
- Altered Bile Acid Profile Associates with Cognitive Impairment in Alzheimer’s Disease – An Emerging Role for Gut Microbiome (2018, background): “The APP transgenic mouse model of AD had a drastically altered gut microbiome composition compared towild-type mice [15].”
- Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis (2019, background): “Anti-Aβ effects could be blocked by reconstruction of these germ-free APP mice with microbiota from conventional mice [184].”
- Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020, background): “The abundance of microbes such as Helicobacteraceae, Desulfovibrionaceae, Odoribacter and Helicobacter is elevated in APP/PS1 transgenic (Tg) animals, whereas microbes such as Firmicutes, Verrucomicrobia, Proteobacteria, Actinobacteria are reduced in Tg animals [591].”