ArticleJournal of diabetes2024
GSK-3β activation mediates apolipoprotein E4-associated cognitive impairment in type 2 diabetes mellitus: A multicenter, cross-sectional study.
Article in Journal of diabetes, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 13 citations in OpenAlex.
- ApoE4 as a Therapeutic Target in Epilepsy: From Pathogenic Mechanisms to Precision Medicine.CNS neuroscience & therapeutics · 2026Review
- Isoorientin inhibits oxidative stress to ameliorate cognitive dysfunction in type 2 diabetes mice via GSK3β/Nrf2 axis.Metabolic brain disease · 2026Article
- Apolipoprotein E4 in Alzheimer's Disease: Role in Pathology, Lipid Metabolism, and Drug Treatment.International journal of molecular sciences · 2026Review
- The Synergistic Role of ApoE4 and GSK3β in Alzheimer's Disease: Pathological Mechanisms and Therapeutic Implications.Molecular neurobiology · 2025Review
- ApoE4 Upregulates GSK-3β to Aggravate Alzheimer-Like Pathologies and Cognitive Impairment in Type 2 Diabetic Mice.CNS neuroscience & therapeutics · 2025Article
- Higher glycated hemoglobin amplifies the effect of apolipoprotein E epsilon 4-related cognition and olfaction impairments in type 2 diabetes.World journal of diabetes · 2025Article
- The multifaceted roles of apolipoprotein E4 in Alzheimer's disease pathology and potential therapeutic strategies.Cell death discovery · 2025Review
- Aripiprazole alleviates the high prolactin levels induced by amisulpride via distinct molecular mechanisms: a network pharmacology and molecular docking study.BMC psychiatry · 2025Article
- Article
- CRISPRi-based screens in iAssembloids to elucidate neuron-glia interactions.bioRxiv : the preprint server for biology · 2024Article
- Updates in Alzheimer's disease: from basic research to diagnosis and therapies.Translational neurodegeneration · 2024Review
- GSK-3β activation mediates apolipoprotein E4-associated cognitive impairment in type 2 diabetes mellitus: A multicenter, cross-sectional study.Journal of diabetes · 2024Article
- Association of glycogen synthase kinase-3β with cognitive impairment in type 2 diabetes patients: a six-year follow-up study.Frontiers in endocrinology · 2024Article
- The impact ofAlzheimer's & dementia (Amsterdam, Netherlands)Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 7 institutions in 2 countries.
Funding
Abstract
aimBoth the activation of glycogen synthase kinase-3β (GSK-3β) and the presence of ApoE ε4 genotype have been found to respectively correlate with cognitive decline in patients with type 2 diabetes mellitus (T2DM), who further show a high incidence of developing Alzheimer's disease. However, the relationship between ApoE ε4 and GSK-3β in the cognitive impairment of T2DM patients remains unclear.
methodsApoE genotypes and platelet GSK-3β level were measured in 1139 T2DM patients recruited from five medical centers in Wuhan, China. Cognitive functions were assessed by Mini-Mental State Examination (MMSE). The association and the relationships among apolipoprotein E (ApoE) genotypes, GSK-3β activity and cognitive function were analyzed by regression and mediating effect analyses, respectively.
resultsT2DM patients with ApoE ε4 but not ApoE ε2 haplotype showed poorer cognitive function and elevated platelet GSK-3β activity, when using ApoE ε3 as reference. The elevation of GSK-3β activity was positively correlated the diabetes duration, as well as plasma glycated hemoglobin (HbA1c) and glucose levels. Moreover, correlation and regression analysis also revealed significant pairwise correlations among GSK-3β activity, ApoE gene polymorphism and cognitive function. Lastly, using Baron and Kenny modeling, we unveiled a mediative role of GSK-3β activity between ApoE ε4 and cognitive impairment.
conclusionWe reported here that the upregulation of GSK-3β activity mediates the exacerbation of cognitive impairment by ApoE ε4-enhanced cognitive impairment in T2DM patients, suggesting GSK-3β inhibitors as promising drugs for preserving cognitive function in T2DM patients, especially to those with ApoE ε4 genotype.
Indexed as
Identifiers
What OpenQuestion holds
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.