ArticleThe EMBO journal2021
Gut inflammation triggers C/EBPβ/δ-secretase-dependent gut-to-brain propagation of Aβ and Tau fibrils in Alzheimer's disease.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- C/EBPβ: A transcription factor associated with the irreversible progression of Alzheimer's disease.CNS neuroscience & therapeutics · 2024Pooled it
- The microbiota-proteostasis axis: implications in neurodegenerative diseases.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Bidirectional communication between the gut microbiota and the central nervous system.Neural regeneration research · 2026Article
- Distinct factors drive the progression of tau pathology in Alzheimer's disease.Fundamental research · 2026Review
- A Comprehensive Review of the Gut-Microbiota-Brain Axis in Alzheimer's Disease: From Pathophysiology to Potential Therapies.Pathogens (Basel, Switzerland) · 2026Review
- A Question of Origins: Non-neuronal Sources of Amyloid-β.Neuroscience bulletin · 2026Review
- Translocation of bacteria from the gut to the brain in mice.PLoS biology · 2026Article
- Brain-gut-microbiota axis: a review on the bidirectional regulatory mechanisms between gut microbiota and brain and their disease interactions.Frontiers in microbiology · 2026Review
- Tuft Cells in the Gut Limit Cognitive Disorders by Regulating Gut Homeostasis.Cellular and molecular gastroenterology and hepatology · 2026Article
- Microbiota-Gut-Brain Axis in Neurodegenerative Diseases: The Role of Bacterial Amyloids.Cellular and molecular gastroenterology and hepatology · 2026Review
- Molecular links between inflammatory bowel disease and Alzheimer's disease through immune signaling and inflammatory pathways.World journal of gastroenterology · 2025Review
- TNF as a mediator of metabolic inflammation and body-brain interaction in obesity-driven neuroinflammation and neurodegeneration.Ageing research reviews · 2025Review
- Fundamental role of brain-organ interaction in behavior-driven holistic homeostasis.Fundamental research · 2025Review
- Huang-Lian-Jie-Du decoction alleviates cognitive impairment in periodontitis rats through restoring microbiota-gut-brain axis and inhibiting neuroinflammation via TLR4/NF-κB pathway.Chinese medicine · 2025Article
- [18F]flutemetamol uptake in the colon of a memory clinic population and its association with brain amyloidosis and the gut microbiota profile: an exploratory study.European journal of nuclear medicine and molecular imaging · 2025Article
- A Systems Biology Approach to Memory Health: Integrating Network Pharmacology, Gut Microbiota, and Multi-Omics for Health Functional Foods.International journal of molecular sciences · 2025Review
- Role of Peripheral NLRP3 Inflammasome in Cognitive Impairments: Insights of Non-central Factors.Molecular neurobiology · 2025Review
- Association between self-reported multimorbidity and longitudinal brain Aβ deposition in Alzheimer's disease.Nature communications · 2025Article
- Clostridioides difficile Infection in Aged Mice Decreases Memory Function, Which Can Be Protected with Alanyl-Glutamine Supplementation.The Journal of nutrition · 2025Article
- Buyang Huanwu Decoction Modulates the Gut Microbiota-C/EBPβ/AEP Axis to Ameliorate Cognitive Impairment in Alzheimer's Disease Mice.CNS neuroscience & therapeutics · 2025Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Inflammation plays an important role in the pathogenesis of Alzheimer's disease (AD). Some evidence suggests that misfolded protein aggregates found in AD brains may have originated from the gut, but the mechanism underlying this phenomenon is not fully understood. C/EBPβ/δ-secretase signaling in the colon was investigated in a 3xTg AD mouse model in an age-dependent manner. We applied chronic administration of 1% dextran sodium sulfate (DSS) to trigger gut leakage or colonic injection of Aβ or Tau fibrils or AD patient brain lysates in 3xTg mice and combined it with excision/cutting of the gut-brain connecting vagus nerve (vagotomy), in order to explore the role of the gut-brain axis in the development of AD-like pathologies and to monitor C/EBPβ/δ-secretase signaling under those conditions. We found that C/EBPβ/δ-secretase signaling is temporally activated in the gut of AD patients and 3xTg mice, initiating formation of Aβ and Tau fibrils that spread to the brain. DSS treatment promotes gut leakage and facilitates AD-like pathologies in both the gut and the brain of 3xTg mice in a C/EBPβ/δ-secretase-dependent manner. Vagotomy selectively blunts this signaling, attenuates Aβ and Tau pathologies, and restores learning and memory. Aβ or Tau fibrils or AD patient brain lysates injected into the colon propagate from the gut into the brain via the vagus nerve, triggering AD pathology and cognitive dysfunction. The results indicate that inflammation activates C/EBPβ/δ-secretase and initiates AD-associated pathologies in the gut, which are subsequently transmitted to the brain via the vagus nerve.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.