Zebrafish study provides evidence forouter membrane vesicles eliciting Alzheimer's disease-like pathologies.

Abstract

INTRODUCTION: Periodontitis has been epidemiologically linked to an increased risk of Alzheimer's disease (AD), yet the mechanistic contribution of periodontal pathogens remains insufficiently understood. Building on our previous findings thatouter membrane vesicles (OMVs) induce cardiovascular dysfunction, this study investigates whether these vesicles also drive AD-related pathology using the zebrafish model. METHODS: We microinjectedOMVs into the common cardinal vein of zebrafish larvae to evaluate locomotor behavior, brain injury, and neuroinflammatory responses. Integrated proteomic and transcriptomic analyses were performed to identify alterations in AD-associated pathways, and acetylcholinesterase activity along with Aβ1-42 plaque accumulation were quantified to validate hallmark AD phenotypes. RESULTS: OMV exposure resulted in significant neurotoxicity, locomotor deficits, and robust neuroinflammation, accompanied by pronounced dysregulation of AD-related molecular pathways. Notably, OMVs markedly increased acetylcholinesterase activity and promoted Aβ1-42 deposition in larval brains. DISCUSSION: These findings demonstrate thatOMVs act as potent inducers of neuronal damage and AD-like pathological features, providing mechanistic insight into how periodontal pathogens may contribute to neurodegenerative disease progression.