Extracellular Vesicles in Alzheimer’s Disease: Dual Roles in Pathogenesis, Promising Avenues for Diagnosis and Therapy

TL;DR

Extracellular vesicles (EVs) play both harmful and helpful roles in Alzheimer’s disease, offering potential for new diagnostics and therapies.

Contribution

This review highlights the dual roles of EVs in AD pathogenesis and their potential as diagnostic biomarkers and therapeutic tools.

Findings

EVs can spread toxic proteins like Aβ and tau, contributing to Alzheimer’s progression.

EVs from stem cells may protect neurons by clearing toxic proteins and reducing inflammation.

Engineered EVs and new technologies like microfluidic chips could improve AD diagnosis and treatment.

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tau tangles, chronic neuroinflammation, and synaptic loss, leading to cognitive decline. Extracellular vesicles (EVs)—lipid bilayer nanoparticles secreted by nearly all cell types—have emerged as critical mediators of intercellular communication, playing a complex dual role in both the pathogenesis and potential treatment of AD. This review generally delineates two opposite roles of EVs in pathogenesis and potential treatment of AD. On one hand, EVs derived from neurons, astrocytes, microglia and oligodendrocytes can propagate toxic proteins (Aβ, tau) and inflammatory signals, thereby accelerating disease progression. On the other hand, EVs—especially those from mesenchymal stem cells (MSCs)—exert neuroprotective effects by facilitating toxic protein clearance, modulating immune responses, preserving synaptic integrity, and alleviating oxidative stress. The cargo-carrying function of EVs gives them considerable diagnostic value. The associated cargos such as proteins and microRNAs (miRNAs) in the EVs may serve as minimally invasive biomarkers for early detection and monitoring of AD. Therapeutically, engineered EVs, including those incorporating CRISPR/Cas9-based genetic modification, are being developed as sophisticated delivery platforms for targeting core AD pathologies. Furthermore, this review highlights emerging technologies such as microfluidic chips and focused ultrasound (FUS), discussing their potential to enhance the translational prospects of EV-based early diagnostic and treatment for AD.

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