Therapeutic and Diagnostic Roles of MSC-Derived Exosomes in Alzheimer's Disease

Alzheimer's disease (AD), the leading cause of dementia, is characterized by amyloid-β accumulation, tau hyperphosphorylation, neuroinflammation, and synaptic failure, with no curative therapies available. This review aims to explore innovative therapeutic and diagnostic strategies, focusing on mesenchymal stem cell-derived exosomes (MSC-exos) as potential disease-modifying agents.

The review synthesizes current evidence on the regenerative, immunomodulatory, and neuroprotective properties of mesenchymal stem cells (MSCs) and their exosomes. It examines how MSC-exos, as nanosized extracellular vesicles carrying proteins, lipids, and nucleic acids, interact with the central nervous system to modulate disease pathways.

MSC-exos can cross the blood-brain barrier (BBB), deliver neurotrophic factors, modulate microglial activity, enhance amyloid clearance, and support neuronal survival and synaptic plasticity. They also hold promise as biomarkers by reflecting central nervous system pathology in peripheral biofluids. Early clinical trials using MSCs from bone marrow, adipose tissue, and umbilical cord show safety and feasibility, with exosome-based approaches offering scalable, cell-free alternatives.

MSC-derived exosomes present a promising avenue for both therapeutic intervention and early diagnosis in AD, offering neuroprotective, anti-inflammatory, and pro-regenerative effects. However, further progress requires addressing challenges such as exosome isolation standardization, cargo characterization, and regulatory considerations to enable their translation into clinical practice.