Degradation of perineuronal nets in hippocampal CA2 explains the loss of social cognition memory in Alzheimer's disease.

ABSTRACT:

Introduction

Loss of social cognition memory impairs Alzheimer's disease (AD) patients to recognize family members, friends, and caregivers. We investigate the role of perineuronal nets (PNNs), specialized coats of extracellular matrix around hippocampal CA2 neurons in AD-associated social memory impairments.

Methods

We utilized 5XFAD mouse model of AD and employed immunohistochemistry, microscopy, bulk RNA-sequencing, animal behavior, gene-knockout, and drug-treatment approaches.

Results

AD mice showed profound disruption of CA2 PNNs with concomitant impairment of social cognition memory. Genetic or enzymatic CA2 PNN disruption in wild-type mice mimicked these impairments. Transcriptomic analysis shows upregulation of PNN-cleaving matrix metalloproteinases (MMP) in A

SUBMITTER: Chaunsali L 

PROVIDER: S-EPMC12541281 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature