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The role of insulin resistance and APOE genotype on blood–brain barrier integrity in Alzheimer's disease
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The role of insulin resistance and APOE genotype on blood–brain barrier integrity in Alzheimer's disease
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Journal Article
The role of insulin resistance and APOE genotype on blood–brain barrier integrity in Alzheimer's disease
2025
Overview
INTRODUCTION Growing evidence suggests a connection between insulin resistance and apolipoprotein E (APOE) genotype in Alzheimer's disease (AD) pathogenesis, but the mechanisms are unclear. We examined effects of insulin resistance and APOE genotype on blood–brain barrier (BBB) integrity in AD. METHODS BBB integrity was measured in 196 biologically‐confirmed non‐diabetic patients with AD evaluating CSF/serum albumin ratio, kappa and lambda free light chains (FLCs). Insulin resistance was assessed using triglyceride–glucose index (TyG). The impact of TyG on BBB integrity, and its interaction with APOE genotypes, was analyzed using multivariate models. RESULTS Sixty‐four percent of patients with AD showed altered TyG, with the 21.8% classified as high TyG. TyG subgroups were associated with BBB abnormalities, with similar AD clinical and biomarkers profile. A significant interaction between TyG and APOE ε4/ε4 genotype on BBB permeability was found in multivariate analyses. DISCUSSION Insulin resistance is a common feature in non‐diabetic AD and correlates with altered BBB permeability, interacting synergistically with APOE genotype. Highlights Insulin resistance and apolipoprotein E (APOE) genotype are well‐recognized risk factors for Alzheimer's disease (AD). Insulin resistance shows high prevalence in patients with AD. Insulin resistance is related to damage in blood–brain barrier (BBB) integrity. The association between the triglyceride–glucose (TyG) index and BBB permeability varies in relation to APOE genotype; patients with the APOE ε4/ε4 displayed higher BBB permeability.
Publisher
John Wiley and Sons Inc
Subject
/ Alzheimer Disease - cerebrospinal fluid
/ Alzheimer Disease - genetics
/ Alzheimer Disease - pathology
/ Apolipoprotein E4 - genetics
/ Apolipoproteins E - genetics
/ Blood-Brain Barrier - metabolism
/ Blood-Brain Barrier - pathology
/ Blood-Brain Barrier - physiopathology
/ Female
/ Genotype
/ Humans
/ Insulin Resistance - genetics
/ Insulin Resistance - physiology
/ Male
