The role of insulin resistance and APOE genotype on blood–brain barrier integrity in Alzheimer's disease

IF 13 1区医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2025-02-24 DOI:10.1002/alz.14556

Alessandro Padovani, Alice Galli, Elena Bazzoli, Chiara Tolassi, Salvatore Caratozzolo, Bianca Gumina, Alberto Benussi, Ilenia Libri, Tiago Fleming Outeiro, Andrea Pilotto

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Abstract

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.

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.