Systematic review and meta-analysis of engineered exosomes in preclinical Alzheimer's models

Engineered exosomes are modified extracellular vesicles designed to enhance targeting and cargo delivery, and they have been proposed as a therapeutic strategy for Alzheimer's disease. We systematically reviewed preclinical animal studies evaluating engineered exosomes, synthesized evidence from comparisons with disease models and with natural exosomes, and reported the study in accordance with the PRISMA 2020 checklist. Outcomes included spatial learning and memory assessed by the Morris water maze, amyloid beta pathology, tau phosphorylation, and neuroinflammatory markers. Random effects meta-analyses suggested that engineered exosomes improved Morris water maze performance and reduced amyloid beta burden and pro-inflammatory cytokines compared with natural exosomes, whereas evidence regarding tau phosphorylation was limited and largely qualitative, and the overall certainty of evidence was low to very low. These findings support further investigation of engineered exosomes, but conclusions should be interpreted cautiously until confirmed by rigorously designed and blinded preclinical studies and clinical trials with standardized protocols.