Fatemeh Ghasemzadeh
1,2 
, Akbar Mousakhani
3,2, Mohammad Karimipour
1,2,4* 1 Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
2 Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran
3 Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
4 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Abstract
Alzheimer’s disease (AD) stands as a formidable, age-related neurodegenerative disorder that is marked by the relentless degeneration of diverse neuronal cell types. This degeneration leads to profound losses in neural tissue, disruption of synaptic networks, cerebral atrophy, and a debilitating decline in cognitive function. Accordingly, the multifaceted nature of AD necessitates a robust and comprehensive therapeutic approach. Although current pharmacological treatments mainly focus on modulating acetylcholine levels through the inhibition of acetylcholinesterase, they only provide symptomatic relief and fail to alter the disease’s relentless progression. In this context, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) emerge as a groundbreaking therapeutic strategy with remarkable potential. These vesicles can modulate neuroinflammation, influence immunological responses, orchestrate microglial activation, and reduce oxidative stress, thereby slowing AD progression. The inflammatory microenvironment plays a pivotal role in AD pathogenesis, with proinflammatory cytokines contributing to neurotoxicity and neuronal apoptosis. Moreover, due to their ability to cross the blood-brain barrier, MSC-EVs are considered key players in delivering therapeutic effects directly within the central nervous system. More precisely, they promote neural tissue regeneration, stimulate neurogenesis, enhance the reorganization of neuronal circuits, and improve synaptic plasticity, thereby fostering essential functional recovery. Therefore, this review highlights the transformative potential of MSCs-EVs in combating the progression of AD, presenting them as a vital pathway for the innovative treatment of neurodegenerative disorders.