Exosomes in Alzheimer's disease: From pathogenesis to therapeutics-A comprehensive review of diagnostic and drug delivery applications.

Alzheimer's disease (AD) is still a major unmet medical challenge, with limited treatment options and a critical need for early diagnostics. Exosomes, nanoscale extracellular vesicles with a lipid bilayer, are pivotal players in intercellular communication and promising tools for AD management. Their unique ability to cross the bloodbrain barrier, low immunogenicity, and ability for cargo delivery make them ideal candidates for targeted drug delivery. This review comprehensively examines the biology of exosomes-including their structure, biogenesis, release, and uptake-and evaluates advanced methods for their isolation, purification, and characterization. We highlight their dual role in AD pathogenesis, where they can propagate pathological proteins such as amyloid-β and tau, and in therapeutic applications, where engineered exosomes deliver neuroprotective agents. Furthermore, exosomal biomarkers in biofluids show significant potential for noninvasive early diagnosis. Recent advances in loading strategies and surface engineering have been discussed, alongside challenges in scalability and safety. This synthesis bridges current knowledge with future directions, emphasizing the translational potential of exosomes in AD therapeutics and diagnostics.