Abstract
The development of novel treatments that restore brain function and improve patient outcomes for Alzheimer's disease (AD) is necessary, given the complications and lack of improvement in recently approved amyloid beta (Aβ)-targeting drugs. Cell-derived extracellular vesicles (EVs) have been found to improve cognitive function through reduced inflammation, oxidative stress, and apoptosis, restoring neuronal and blood-brain barrier function, and inhibiting Aβ and phosphorylated tau build-up in the brain. Given the recent emergence of EVs into clinical trials, it is essential to provide the field with an update on proposed mechanisms of action, gaps in knowledge for further study, and recommendations for producing EVs with high therapeutic efficacy to ensure success in subsequent clinical trials. This systematic review summarizes original research to date that reports effects of mammalian cell-derived EVs for the treatment of AD. Evidence of therapeutic benefits and reported mechanisms of action are discussed. Further, methods for engineering EVs to increase their therapeutic efficacy and produce high-quality EVs relevant to the AD field are outlined. The quality of evidence is discussed in terms of reporting guidelines from the Minimal Information for Studies of Extracellular Vesicles (MISEV). The review further discusses current preclinical AD models and provides direction to improve the quality of AD models for testing novel therapeutics.