ArticleFrontiers in aging neuroscience2020
Cerebral Fructose Metabolism as a Potential Mechanism Driving Alzheimer's Disease.
Article in Frontiers in aging neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- Nanoparticle-enriched mass spectrometry enables comprehensive plasma proteomics and reveals novel candidates for mild cognitive impairment.Scientific reports · 2026Article
- Gut-brain axis: beneficial impact of Shouchella clausii spores on fructose induced dysfunction is associated with modulation of the deoxycholic acid - TGR5 pathway.Molecular medicine (Cambridge, Mass.) · 2026Article
- Fructose Intake Is Associated with Brain Metabolic Reprogramming and Exacerbation of Alzheimer-like Alterations in APP/PS1 Mice.International journal of molecular sciences · 2026Article
- Common metabolic, environmental, and molecular mechanisms underlying neurodevelopmental and neurodegenerative disorders.Frontiers in neurology · 2026Review
- Impact of common variants on brain gene expression from RNA to protein to schizophrenia risk.Nature communications · 2025Article
- Identification of a common ketohexokinase-dependent link driving alcohol intake and alcohol-associated liver disease in mice.Nature metabolism · 2025Article
- Effect ofBiomolecules · 2025Article
- Progress in Understanding the Regulation of Glucose and Fructose Metabolism.Annual review of nutrition · 2025Review
- Gastrodin attenuates high fructose-induced sweet taste preference decrease by inhibiting hippocampal neural stem cell ferroptosis.Journal of advanced research · 2025Article
- Diet, Mitochondrial Dysfunction, Vascular Endothelial Damage, and the Microbiome: Drivers of Ocular Degenerative and Inflammatory Diseases.Ophthalmology and therapy · 2025Review
- Elucidating neural molecular mechanisms underlying metabolic disorders-induced neuropsychiatric disorders in mice on prolonged high fructose diet.Metabolic brain disease · 2025Article
- Do microglia metabolize fructose in Alzheimer's disease?Journal of neuroinflammation · 2025Review
- Molecular pathogenesis of Alzheimer's disease onset in a mouse model: effects of cannabidiol treatment.Frontiers in neuroscience · 2025Article
- Nicotinamide Mononucleotide (NMN) Works in Type 2 Diabetes through Unexpected Effects in Adipose Tissue, Not by Mitochondrial Biogenesis.International journal of molecular sciences · 2024Article
- Untargeted Metabolomic Profiling Reveals Differentially Expressed Serum Metabolites and Pathways in Type 2 Diabetes Patients with and without Cognitive Decline: A Cross-Sectional Study.International journal of molecular sciences · 2024Article
- Review
- Differential responses of primary neuron-secreted MCP-1 and IL-9 to type 2 diabetes and Alzheimer's disease-associated metabolites.bioRxiv : the preprint server for biology · 2023Article
- Ketohexokinase-dependent metabolism of cerebral endogenous fructose in microglia drives diabetes-associated cognitive dysfunction.Experimental & molecular medicine · 2023Article
- The fructose survival hypothesis for obesity.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Cholesterol, Amyloid Beta, Fructose, and LPS Influence ROS and ATP Concentrations and the Phagocytic Capacity of HMC3 Human Microglia Cell Line.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
The loss of cognitive function in Alzheimer's disease is pathologically linked with neurofibrillary tangles, amyloid deposition, and loss of neuronal communication. Cerebral insulin resistance and mitochondrial dysfunction have emerged as important contributors to pathogenesis supporting our hypothesis that cerebral fructose metabolism is a key initiating pathway for Alzheimer's disease. Fructose is unique among nutrients because it activates a survival pathway to protect animals from starvation by lowering energy in cells in association with adenosine monophosphate degradation to uric acid. The fall in energy from fructose metabolism stimulates foraging and food intake while reducing energy and oxygen needs by decreasing mitochondrial function, stimulating glycolysis, and inducing insulin resistance. When fructose metabolism is overactivated systemically, such as from excessive fructose intake, this can lead to obesity and diabetes. Herein, we present evidence that Alzheimer's disease may be driven by overactivation of cerebral fructose metabolism, in which the source of fructose is largely from endogenous production in the brain. Thus, the reduction in mitochondrial energy production is hampered by neuronal glycolysis that is inadequate, resulting in progressive loss of cerebral energy levels required for neurons to remain functional and viable. In essence, we propose that Alzheimer's disease is a modern disease driven by changes in dietary lifestyle in which fructose can disrupt cerebral metabolism and neuronal function. Inhibition of intracerebral fructose metabolism could provide a novel way to prevent and treat this disease.
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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.