Systemic lipid and glucose modulation differentially affects cognitive function and neuroinflammation in a mouse model of Alzheimer's disease.

ABSTRACT:

Introduction

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by synaptic dysfunction and cognitive decline. Increasing evidence implicates systemic metabolic dysregulation in AD pathogenesis, yet it remains unclear whether modulation of peripheral lipid and glucose metabolism can alter disease progression.

Methods

We investigated the effects of two FDA-approved metabolic agents-Alirocumab, a PCSK9 inhibitor that lowers LDL cholesterol, and Gliclazide, a sulfonylurea that enhances insulin secretion-in male 5xFAD mice, a transgenic model of AD. Animals received chronic treatment for five months. Behavioral testing, hippocampal electrophysiology, ELISA, lipidomics, and adipokine profiling were performed to assess cognitive, synaptic, and molec

SUBMITTER: Kynigopoulos D 

PROVIDER: S-EPMC12426080 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature