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Bacteroidota inhibi...
Bacteroidota inhibit microglia clearance of amyloid-beta and promote plaque deposition in Alzheimer’s disease mouse models
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- Wasén, Caroline, 1990 (author)
- Göteborgs universitet,University of Gothenburg,Harvard Medical School,Chalmers tekniska högskola,Chalmers University of Technology
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- Beauchamp, Leah C. (author)
- Harvard Medical School
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- Vincentini, Julia (author)
- Harvard Medical School
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- Li, Shuqi (author)
- Harvard Medical School
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- LeServe, Danielle S. (author)
- Harvard Medical School
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- Gauthier, Christian (author)
- Harvard Medical School
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- Lopes, Juliana R. (author)
- Harvard Medical School
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- Moreira, Thais G. (author)
- Harvard Medical School
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- Ekwudo, Millicent N. (author)
- Harvard Medical School
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- Yin, Zhuoran (author)
- Harvard Medical School
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- da Silva, Patrick (author)
- Harvard Medical School
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- Krishnan, Rajesh K. (author)
- Harvard Medical School
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- Butovsky, Oleg (author)
- Harvard Medical School
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- Cox, Laura M. (author)
- Harvard Medical School
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- Weiner, Howard L. (author)
- Harvard Medical School
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(creator_code:org_t)
- 2024
- 2024
- English.
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In: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Abstract
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- The gut microbiota and microglia play critical roles in Alzheimer’s disease (AD), and elevated Bacteroides is correlated with cerebrospinal fluid amyloid-β (Aβ) and tau levels in AD. We hypothesize that Bacteroides contributes to AD by modulating microglia. Here we show that administering Bacteroides fragilis to APP/PS1-21 mice increases Aβ plaques in females, modulates cortical amyloid processing gene expression, and down regulates phagocytosis and protein degradation microglial gene expression. We further show that administering Bacteroides fragilis to aged wild-type male and female mice suppresses microglial uptake of Aβ1-42 injected into the hippocampus. Depleting murine Bacteroidota with metronidazole decreases amyloid load in aged 5xFAD mice, and activates microglial pathways related to phagocytosis, cytokine signaling, and lysosomal degradation. Taken together, our study demonstrates that members of the Bacteroidota phylum contribute to AD pathogenesis by suppressing microglia phagocytic function, which leads to impaired Aβ clearance and accumulation of amyloid plaques.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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- By the author/editor
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Wasén, Caroline, ...
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Beauchamp, Leah ...
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Vincentini, Juli ...
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Li, Shuqi
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LeServe, Daniell ...
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Gauthier, Christ ...
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show more...
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Lopes, Juliana R ...
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Moreira, Thais G ...
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Ekwudo, Millicen ...
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Yin, Zhuoran
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da Silva, Patric ...
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Krishnan, Rajesh ...
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Butovsky, Oleg
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Cox, Laura M.
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Weiner, Howard L ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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Nature Communica ...
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Chalmers University of Technology