Evaluation of hippocampal <i>DLGAP2</i> overexpression on cognition, synaptic function, and dendritic spine structure in a translationally relevant AD mouse model.

ABSTRACT:

Introduction

Developing effective therapeutics for Alzheimer's Disease (AD) requires a better understanding of the molecular drivers of the disease. Our previous work nominated DLGAP2 as a modifier of age-related cognitive decline and risk for AD. We tested the hypothesis that overexpression of DLGAP2 in the hippocampus would protect against cognitive and synaptic deficits in a susceptible F1 5XFAD model.

Methods

DLGAP2 was overexpressed in the hippocampus of F1 hybrid 5XFAD and nontransgenic littermates using a viral approach. Cognitive function, electrophysiological properties, and dendritic spine morphology were assessed at 6 and 14 months of age.

Results

DLGAP2 overexpression impaired synaptic plasticity and exacerbated AD-related memory defic

SUBMITTER: Ouellette A 

PROVIDER: S-EPMC12132555 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature