Metabolic stress and age drive inflammation and cognitive decline in mice and humans.

ABSTRACT:

Introduction

Metabolic stressors (obesity, metabolic syndrome, prediabetes, and type 2 diabetes [T2D]) increase the risk of cognitive impairment (CI), including Alzheimer's disease (AD). Immune system dysregulation and inflammation, particularly microglial mediated, may underlie this risk, but mechanisms remain unclear.

Methods

Using a high-fat diet-fed (HFD) model, we assessed longitudinal metabolism and cognition, and terminal inflammation and brain spatial transcriptomics. Additionally, we performed hippocampal spatial transcriptomics and single-cell RNA sequencing of post mortem tissue from AD and T2D human subjects versus controls.

Results

HFD induced progressive metabolic and CI with terminal inflammatory changes, and dysmetabolic, neurodegenerative, and inflamm

SUBMITTER: Elzinga SE 

PROVIDER: S-EPMC11923576 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature