APOE ε4 disrupts neuronal and network-level function in the anterior olfactory nucleus: Influence of age and sex.

ABSTRACT:

Introduction

Apolipoprotein E (APOE) ε4 is the strongest genetic risk factor for sporadic Alzheimer's disease (AD), which features early olfactory dysfunction and pathology. However, how APOE ε4 interacts with age and sex to affect cellular and network function in vulnerable regions such as the anterior olfactory nucleus (AON) remains unclear.

Methods

In vivo recordings in awake transgenic mice were used to assess how APOE ε4, age, and sex interact to influence single-cell excitability and network activity.

Results

APOE ε4 reduces excitability in the AON; adult females show higher excitability than males, a difference that is lost with age. Excitability and network activity vary by genotype and sex, while aging consistently increases network power, underscoring their

SUBMITTER: Uzun C 

PROVIDER: S-EPMC12568776 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature