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Updated: Jul 9, 2025
Quantitative 3D In Silico Modeling q3DISM of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease
Published on: December 26, 2016
Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in
Namkwon Kim1,2, In Gyoung Ju3,4, Seung Ho Jeon2
1Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, Republic of Korea.
Background:
The gut microbiota has recently attracted attention as a pathogenic factor in Alzheimer's disease (AD). Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown.
Methods:
Five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) naïve mice were used to investigate the changes of M cells in the AD environment. Next, to establish the effect of M cell depletion on AD environments, 5xFAD mice and Spib knockout mice were bred, and behavioral and histological analyses were performed when M cell-depleted 5xFAD mice were six or nine months of age.
Results:
In this study, we found that M cell numbers were increased in the colons of 5xFAD and 5xFAD-FMT mice compared to those of wild-type (WT) and WT-FMT mice. Moreover, the level of total bacteria infiltrating the colons increased in the AD-mimicked mice. The levels of M cell-related genes and that of infiltrating bacteria showed a significant correlation. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota, along with decreasing proinflammatory cytokine levels in the colons. M cell depletion ameliorated AD symptoms including amyloid-β accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies, such as memory impairment and excessive neuroinflammation in Spib-/- mice.
Conclusion:
Therefore, our findings provide evidence that the inhibiting M cells can prevent AD progression, with therapeutic implications.
Insights
Inhibiting microfold (M) cells in the gut can prevent Alzheimer's disease (AD) progression. Reducing M cell activity ameliorates AD symptoms and neuroinflammation, suggesting a novel therapeutic target for AD.
Area of Science:
- Neuroscience
- Immunology
- Microbiology
Background:
- Alzheimer's disease (AD) pathogenesis is increasingly linked to gut microbiota alterations.
- Microfold (M) cells in the gut facilitate antigen transport, potentially serving as entry points for pathogens in AD.
- The specific role of M cells in modulating gut environment and brain pathology in AD remains unclear.
Purpose of the Study:
- To investigate the changes in M cells within the AD gut environment.
- To determine the impact of M cell depletion on AD progression and associated pathologies.
Main Methods:
- Utilized 5xFAD mice and 5xFAD-derived fecal microbiota transplantation (FMT) models.
- Employed Spib knockout mice to genetically inhibit M cells in 5xFAD background.
- Conducted behavioral and histological analyses at 6 and 9 months of age.
Main Results:
- Increased M cell numbers and bacterial infiltration observed in the colons of AD-mimicked mice.
- Genetic inhibition of M cells altered gut microbiota composition and reduced colonic inflammation.
- M cell depletion significantly ameliorated AD symptoms, including amyloid-β deposition, microglial dysfunction, neuroinflammation, and memory deficits.
Conclusions:
- Findings indicate that M cells contribute to AD pathogenesis.
- Inhibiting M cells shows potential as a therapeutic strategy to prevent AD progression.
- Targeting M cells may offer a novel approach for AD treatment.
