ArticlePloS one2015
High Fat Diet Enhances β-Site Cleavage of Amyloid Precursor Protein (APP) via Promoting β-Site APP Cleaving Enzyme 1/Adaptor Protein 2/Clathrin Complex Formation.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- A systematic review on the effects of hypercaloric diet in animal models of Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2026Pooled it
- Oral Supplements of Combined Lactobacillus plantarum and Asparagus officinalis Modulate Gut Microbiota and Alleviate High-Fat Diet-Induced Cognitive Deficits and Neurodegeneration in Rats.Probiotics and antimicrobial proteins · 2025Article
- High-Fat Diet-Induced Excessive Accumulation of Cerebral Cholesterol Esters and Microglial Dysfunction Exacerbate Alzheimer's Disease Pathology in APPMolecular neurobiology · 2025Article
- Amyloid-beta metabolism in age-related neurocardiovascular diseases.European heart journal · 2025Review
- Endosomal traffic disorders: a driving force behind neurodegenerative diseases.Translational neurodegeneration · 2024Review
- Endocytosis and Alzheimer's disease.GeroScience · 2024Review
- The Effect of Fat Intake with Increased Omega-6-to-Omega-3 Polyunsaturated Fatty Acid Ratio in Animal Models of Early and Late Alzheimer's Disease-like Pathogenesis.International journal of molecular sciences · 2023Article
- Environmental exposures and the etiopathogenesis of Alzheimer's disease: The potential role of BACE1 as a critical neurotoxic target.Journal of biochemical and molecular toxicology · 2021Review
- Altered Brain Leptin and Leptin Receptor Expression in the 5XFAD Mouse Model of Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2020Article
- High fat diet worsens Alzheimer's disease-related behavioral abnormalities and neuropathology in APP/PS1 mice, but not by synergistically decreasing cerebral blood flow.Scientific reports · 2020Article
- Combination of Omega 3 and Coenzyme Q10 Exerts Neuroprotective Potential Against Hypercholesterolemia-Induced Alzheimer's-Like Disease in Rats.Neurochemical research · 2020Article
- Article
- Peripheral Amyloid Precursor Protein Derivative Expression in Fragile X Syndrome.Frontiers in integrative neuroscience · 2019Article
- TLR4 inhibitor TAK-242 attenuates the adverse neural effects of diet-induced obesity.Journal of neuroinflammation · 2018Article
- Pericyte-derived bone morphogenetic protein 4 underlies white matter damage after chronic hypoperfusion.Brain pathology (Zurich, Switzerland) · 2018Article
- Palmitate-induced C/EBP homologous protein activation leads to NF-κB-mediated increase in BACE1 activity and amyloid beta genesis.Journal of neurochemistry · 2018Article
- Mitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases.International review of cell and molecular biology · 2018Review
- Palmitic Acid-BSA enhances Amyloid-β production through GPR40-mediated dual pathways in neuronal cells: Involvement of the Akt/mTOR/HIF-1α and Akt/NF-κB pathways.Scientific reports · 2017Article
- Reversal of high fat diet-induced obesity improves glucose tolerance, inflammatory response, β-amyloid accumulation and cognitive decline in the APP/PSEN1 mouse model of Alzheimer's disease.Neurobiology of disease · 2017Article
- Palmitate Increases β-site AβPP-Cleavage Enzyme 1 Activity and Amyloid-β Genesis by Evoking Endoplasmic Reticulum Stress and Subsequent C/EBP Homologous Protein Activation.Journal of Alzheimer's disease : JAD · 2017Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Obesity and type 2 diabetes are risk factors of Alzheimer's disease (AD). We reported that a high fat diet (HFD) promotes amyloid precursor protein (APP) cleavage by β-site APP cleaving enzyme 1 (BACE1) without increasing BACE1 levels in APP transgenic mice. However, the detailed mechanism had remained unclear. Here we demonstrate that HFD promotes BACE1/Adaptor protein-2 (AP-2)/clathrin complex formation by increasing AP-2 levels in APP transgenic mice. In Swedish APP overexpressing Chinese hamster ovary (CHO) cells as well as in SH-SY5Y cells, overexpression of AP-2 promoted the formation of BACE1/AP-2/clathrin complex, increasing the level of the soluble form of APP β (sAPPβ). On the other hand, mutant D495R BACE1, which inhibits formation of this trimeric complex, was shown to decrease the level of sAPPβ. Overexpression of AP-2 promoted the internalization of BACE1 from the cell surface, thus reducing the cell surface BACE1 level. As such, we concluded that HFD may induce the formation of the BACE1/AP-2/clathrin complex, which is followed by its transport of BACE1 from the cell surface to the intracellular compartments. These events might be associated with the enhancement of β-site cleavage of APP in APP transgenic mice. Here we present evidence that HFD, by regulation of subcellular trafficking of BACE1, promotes APP cleavage.
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