Cited by 901Alzheimer's disease research and treatmentsGut microbiota and healthNeuroinflammation and Neurodegeneration Mechanisms

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

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Harach, T., Marungruang, N., Duthilleul, N., Cheatham, V., Mc Coy, K. D., Frisoni, G., Neher, J. J., Fåk, F. +3 more·2017·Scientific Reports

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.

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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 measured
  • 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.

    “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”
  • 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.”
  • 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].”
  • 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].”

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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)
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
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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