ArticleMolecular psychiatry2022
High-fat diet-induced diabetes couples to Alzheimer's disease through inflammation-activated C/EBPβ/AEP pathway.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 2 of them syntheses that pooled it.
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Who cites it
53 citing papers in PubMed, 2 syntheses or guidelines pooled it, 67 citations in OpenAlex.
- C/EBPβ as a master regulator of inflammasome signaling in neurodegenerative diseases: mechanisms and therapeutic implications.Frontiers in immunology · 2025Pooled it
- C/EBPβ: A transcription factor associated with the irreversible progression of Alzheimer's disease.CNS neuroscience & therapeutics · 2024Pooled it
- ZBP1-mediated Treg cell dysfunction exacerbates neuroimmune dysregulation in Alzheimer's disease under metabolic stress.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Targeting C/EBPβ/ Calbindin 1 pathway bolsters the neural resilience to tau pathology and improves tau-impaired episodic memory.Molecular psychiatry · 2026Article
- Assessment of the Association of Periodontitis and Diabetes Mellitus with Alzheimer's Disease in a Mouse Model.International journal of molecular sciences · 2026Article
- The transcription factor C/EBPβ promotes hyperglycemia-elicited glycolysis and liver cancer progression.Nature communications · 2026Article
- Neuroprotective potential of esterified indole-3-propionic acid with curcumin against high glucose stress: targeting oxidative damage, Akt/mTOR, and BDNF/TrkB pathways.BMC pharmacology & toxicology · 2026Article
- Neuroinflammation and Secretase Regulation in Alzheimer's Disease: From Molecular Cross-Talk to Multi-Target Therapeutics.International journal of molecular sciences · 2026Review
- Article
- High-Fat Diet and a High Amyloid Load Interact to Induce PKC-α Dependent Synaptic Insulin Resistance.Molecular & cellular proteomics : MCP · 2026Article
- Exercise reverses high-fat diet-induced perivascular adipose tissue dysfunction through modulation of UCP2 and TXNIP/NLRP3 pathways.Journal of physiology and biochemistry · 2026Article
- Sex specific effects of a high fat diet on metabolism, cognition, and pathology in the Tg-SwDI mouse model of Alzheimer's disease.Journal of neuroinflammation · 2026Article
- Association of Triglyceride-to-HDL Cholesterol Ratio with Osteoarthritis: Multicenter Evidence and Application of an Interactive Risk Visualization Tool.Journal of inflammation research · 2026Article
- Neuroprotective effects ofFrontiers in nutrition · 2026Article
- A review of risk factors and intervention measures for comorbidity of diabetes and mental disorders.Frontiers in psychiatry · 2026Review
- The diagnostic value of plasma Aβ42 and Aβ40 in Alzheimer's disease: current status, challenges, and impacting variables.Journal of neurology · 2025Review
- Astrocytes distress triggers brain pathology through induction of δ secretase in a murine model of Alzheimer's disease.Nature communications · 2025Article
- Adipokines at the Metabolic-Brain Interface: Therapeutic Modulation by Antidiabetic Agents and Natural Compounds in Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Treadmill Exercise Modulates the Leptin/LepR/GSK-3β Signalling Pathway to Improve Leptin Sensitivity and Alleviate Neuroinflammation in High-Fat Diet-Fed APP/PS1 Mice.Molecular neurobiology · 2025Article
- Neuroprotection by Nauclea latifolia extract in arsenite & high-fat diet-induced brain stress.Environmental analysis, health and toxicology · 2025Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
Abstract
Diabetes is a risk factor for Alzheimer's disease (AD), which is also called type 3 diabetes with insulin reduction and insulin resistance in AD patient brains. However, the molecular mechanism coupling diabetes to AD onset remains incompletely understood. Here we show that inflammation, associated with obesity and diabetes elicited by high-fat diet (HFD), activates neuronal C/EBPβ/AEP signaling that drives AD pathologies and cognitive disorders. HFD stimulates diabetes and insulin resistance in neuronal Thy1-C/EBPβ transgenic (Tg) mice, accompanied with prominent mouse Aβ accumulation and hyperphosphorylated Tau aggregation in the brain, triggering cognitive deficits. These effects are profoundly diminished when AEP is deleted from C/EBPβ Tg mice. Chronic treatment with inflammatory lipopolysaccharide (LPS) facilitates AD pathologies and cognitive disorders in C/EBPβ Tg but not in wild-type mice, and these deleterious effects were substantially alleviated in C/EBPβ Tg/AEP -/- mice. Remarkably, the anti-inflammatory drug aspirin strongly attenuates HFD-induced diabetes and AD pathologies in neuronal C/EBPβ Tg mice. Therefore, our findings demonstrate that inflammation-activated neuronal C/EBPβ/AEP signaling couples diabetes to AD.
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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.