ArticlePloS one2011
The ε3 and ε4 alleles of human APOE differentially affect tau phosphorylation in hyperinsulinemic and pioglitazone treated mice.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Effect of antidiabetic drugs in Alzheimer´s disease: a systematic review of preclinical and clinical studies.Molecular neurodegeneration · 2025Pooled it
- Obesity affects brain cortex gene expression in an APOE genotype and sex dependent manner.International journal of obesity (2005) · 2024Article
- High-Fat Diets in Animal Models of Alzheimer's Disease: How Can Eating Too Much Fat Increase Alzheimer's Disease Risk?Journal of Alzheimer's disease : JAD · 2024Review
- Effects ofMetabolites · 2023Article
- Therapeutic strategies for tauopathies and drug repurposing as a potential approach.Biochemical pharmacology · 2022Review
- Reassessment of Pioglitazone for Alzheimer's Disease.Frontiers in neuroscience · 2021Review
- Apolipoprotein E4 mediates insulin resistance-associated cerebrovascular dysfunction and the post-prandial response.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Effects of apolipoprotein E on nutritional metabolism in dementia.Current opinion in lipidology · 2019Review
- Association of ApoE Genetic Polymorphism and Type 2 Diabetes with Cognition in Non-Demented Aging Chinese Adults: A Community Based Cross-Sectional Study.Aging and disease · 2018Article
- Transcriptional regulation of APP by apoE: To boldly go where no isoform has gone before: ApoE, APP transcription and AD: Hypothesised mechanisms and existing knowledge gaps.BioEssays : news and reviews in molecular, cellular and developmental biology · 2017Review
- Apolipoprotein E4 and Insulin Resistance Interact to Impair Cognition and Alter the Epigenome and Metabolome.Scientific reports · 2017Article
- Altered cerebral insulin response in transgenic mice expressing the epsilon-4 allele of the human apolipoprotein E gene.Psychoneuroendocrinology · 2017Article
- Toll-interacting protein deficiency promotes neurodegeneration via impeding autophagy completion in high-fat diet-fed ApoEBrain, behavior, and immunity · 2017Article
- Combination treatment with leptin and pioglitazone in a mouse model of Alzheimer's disease.Alzheimer's & dementia (New York, N. Y.) · 2017Article
- Finding novel distinctions between the sAPPα-mediated anabolic biochemical pathways in Autism Spectrum Disorder and Fragile X Syndrome plasma and brain tissue.Scientific reports · 2016Article
- Role of insulin resistance in Alzheimer's disease.Metabolic brain disease · 2015Review
- Role of anti-diabetic drugs as therapeutic agents in Alzheimer's disease.EXCLI journal · 2015Review
- Neuroinflammation is not a Prerequisite for Diabetes-induced Tau Phosphorylation.Frontiers in neuroscience · 2015Article
- Therapeutic Actions of the Thiazolidinediones in Alzheimer's Disease.PPAR research · 2015Review
- Expression of human apolipoprotein E4 reduces insulin-receptor substrate 1 expression and Akt phosphorylation in the ageing liver.FEBS open bio · 2014Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundImpaired insulin signalling is increasingly thought to contribute to Alzheimer's disease (AD). The ε4 isoform of the APOE gene is the greatest genetic risk factor for sporadic, late onset AD, and is also associated with risk for type 2 diabetes mellitus (T2DM). Neuropathological studies reported the highest number of AD lesions in brain tissue of ε4 diabetic patients. However other studies assessing AD pathology amongst the diabetic population have produced conflicting reports and have failed to show an increase in AD-related pathology in diabetic brain. The thiazolidinediones (TZDs), peroxisome proliferator-activated receptor gamma agonists, are peripheral insulin sensitisers used to treat T2DM. The TZD, pioglitazone, improved memory and cognitive functions in mild to moderate AD patients. Since it is not yet clear how apoE isoforms influence the development of T2DM and its progression to AD, we investigated amyloid beta and tau pathology in APOE knockout mice, carrying human APOEε3 or ε4 transgenes after diet-induced insulin resistance with and without pioglitazone treatment.
methodsMale APOE knockout, APOEε3-transgenic and APOEε4-transgenic mice, together with background strain C57BL6 mice were kept on a high fat diet (HFD) or low fat diet (LFD) for 32 weeks, or were all fed HFD for 32 weeks and during the final 3 weeks animals were treated with pioglitazone or vehicle.
resultsAll HFD animals developed hyperglycaemia with elevated plasma insulin. Tau phosphorylation was reduced at 3 epitopes (Ser396, Ser202/Thr205 and Thr231) in all HFD, compared to LFD, animals independent of APOE genotype. The introduction of pioglitazone to HFD animals led to a significant reduction in tau phosphorylation at the Ser202/Thr205 epitope in APOEε3 animals only. We found no changes in APP processing however the levels of soluble amyloid beta 40 was reduced in APOE knockout animals treated with pioglitazone.
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