Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota
Open accessAbstract
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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Antibiotic-induced depletion of gut microbiota in AD mouse models has been shown to reduce amyloid accumulation and modulate microglial activation.
“Notably, antibiotic-induced depletion of gut microbiota in AD mouse models has been shown to reduce amyloid accumulation and modulate microglial activation65.”
From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [65]
The Discussion reports reduced amyloid pathology and microgliosis in germ-free APPPS1 mice. But these mice were raised without gut microbiota, not depleted with antibiotics. The paper mentions a separate antibiotic study in its introductory text, but does not establish the claimed combination of reduced amyloid accumulation and altered microglial activation from antibiotic treatment. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThis protection was diminished following FMT from 12-month-old conventionally raised APP/PS1-21 mice to 4-month-old GF APP/PS1-21 mice.
“However, this protection was diminished following FMT from 12-month-old conventionally raised APP/PS1-21 mice to 4-month-old GF APP/PS1-21 mice.198”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [198]
Gut microbiota from APP/PS1 mice differs significantly compared to wild-type mice.
“For example, gut microbiota from APP/PS1 mice differs significantly compared to wild-type mice.”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [591]
In APP/PS1 transgenic animals, abundance of Helicobacteraceae, Desulfovibrionaceae, Odoribacter and Helicobacter is elevated, whereas Firmicutes, Verrucomicrobia, Proteobacteria, Actinobacteria are reduced.
“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].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [591]
A variety of genetic and environmental factors have been implicated in AD etiopathogenesis, including contributions from gut microbiota.
“A variety of genetic and environmental factors have been implicated in AD etiopathogenesis, including contributions from gut microbiota [13–15].”
From The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer’s disease (2018) · cites this paper as [13]
Fecal transplantation from conventionally-raised APP/PS1 mice into germ-free APP/PS1 hosts dramatically increased cerebral Aβ pathology in the hosts.
“Fecal transplantation from conventionally-raised APP/PS1 mice into GF APP/PS1 hosts dramatically increased cerebral Aβ pathology in the hosts (161).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [161]
Germ-free APP/PS1 transgenic mice have reduced Aβ levels in the brain and blood and reduced amyloid load compared to conventionally-raised APP/PS1 mice.
“Importantly, GF-APP/PS1 transgenic mice have reduced Aβ levels in the brain and blood and reduced amyloid load compared to conventionally-raised APP/PS1 mice (161).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [161]
These results strongly supported a microbiota involvement in the development of Alzheimer's disease in Alzheimer's disease-susceptible animal models.
“Altogether, these results strongly supported a microbiota involvement in the development of AD in AD-susceptible animal models (161).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [161]
APP/PS1 double transgenic mice show a remarkable shift in gut microbiota composition compared to healthy wild-type mice.
“APP/PS1 double transgenic mice, which express special neurons in the CNS with a chimeric mouse/human amyloid precursor protein (APP) and a mutant human presenilin 1 (PS1), show a remarkable shift in the gut microbiota composition compared to healthy wild-type mice (161).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [161]
Fewer Firmicutes (Akkermansia and Rikenellaceaea) but more Bacteroidetes (S24-7) were identified in conventionally-raised APP/PS1 mice compared to wild-type littermate controls.
“Fewer Firmicutes (Akkermansia and Rikenellaceaea) but more Bacteroidetes (S24-7) were identified in conventionally-raised APP/PS1 mice compared to wild-type littermate controls (161).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [161]
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- Authors
- Harach, T., Marungruang, N., Duthilleul, N., Cheatham, V., Mc Coy, K. D., Frisoni, G., Neher, J. J., Fåk, F., Jucker, M., Lasser, T., & Bolmont, T.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Lund University (SE)
- University of Geneva (CH)
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Bolmont, T.
- Venue
- Scientific Reports
- Published
- 2017-02-08
- Volume
- 7
- Issue
- 1
- Pages
- 41802-41802
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5297247
- OpenAlex
- W2587539025
- Cited by
- 901
- References
- 47
- Citations by year
- 2026: 61 · 2025: 99 · 2024: 113 · 2023: 114 · 2022: 122 · 2021: 128 · 2020: 113 · 2019: 79 · 2018: 51 · 2017: 20
- FWCI
- 53.23
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-07-10)
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Lund University Publications (Lund University) (submittedVersion)
- DZNE Pub (submittedVersion, cc-by)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Mats Paulssons Stiftelse
- Gebert Rüf Stiftung
- Direktör Albert Påhlssons Stiftelse
- Università degli Studi di Brescia
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid-beta pathology, gut microbiota, germ-free mice, microbiota transfer, fecal microbiota, 16S rRNA gene sequencing, neurodegeneration
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