Exosome-Based Therapeutics in Alzheimer's Disease: Translational Perspectives Beyond Conventional Therapies

Alzheimer's disease (AD) remains a major neurodegenerative disorder lacking effective long-term disease-modifying therapies. Current pharmacological approaches provide primarily symptomatic benefit, while recently approved anti-amyloid monoclonal antibodies offer only modest clinical efficacy and are constrained by safety concerns, high costs, and limited blood-brain barrier (BBB) penetration. In this context, exosome-based strategies have emerged as potential therapeutic platforms in AD research. As endogenous nanovesicles, exosomes exhibit favorable biocompatibility, intrinsic BBB-crossing capacity, and the ability to deliver diverse therapeutic cargo across multiple pathological pathways. Through bioengineering approaches, exosomes may additionally be optimized for targeted brain delivery and therapeutic personalization. Nevertheless, despite their conceptual and preclinical advantages, exosome-based therapies remain at an early translational stage, with unresolved challenges related to large-scale production, standardization, biodistribution, and long-term safety. This review provides a comparative translational analysis of conventional and exosome-based therapeutic strategies in AD, focusing on mechanistic targeting, delivery efficiency, safety and tolerability, therapeutic personalization, and translational readiness. We critically evaluate the extent to which exosome-based platforms may address the limitations of current therapies while highlighting the key barriers that continue to limit their clinical translation and real-world applicability.