Extracellular Vesicles in Alzheimer's Disease: Mechanisms, Biomarkers, and Therapeutic Engineering.

Extracellular vesicles (EVs) are nanoscale membrane-bound particles that mediate intercellular communication by transferring proteins, nucleic acids, lipids, and metabolites. Increasing evidence implicates EVs in Alzheimer's disease (AD) pathogenesis through the propagation of amyloid-β, tau, and neuroinflammatory signals across neural and glial networks. In parallel, EVs isolated from biofluids have emerged as promising sources of disease-associated biomarkers and potential therapeutic carriers. This review aims to synthesize current evidence on EV-mediated mechanisms in AD, evaluate the diagnostic value of EV-associated biomarkers, and discuss emerging EV-based and bioengineered therapeutic strategies. We summarize how EVs derived from neurons, astrocytes, microglia, and peripheral cells contribute to amyloid-β and tau spread, neuroinflammation, synaptic dysfunction, and metabolic stress in AD. Disease-associated alterations in EV cargo from blood, cerebrospinal fluid, and urine are critically assessed for biomarker applications. We further highlight advances in EV bioengineering, including cargo loading, surface modification, targeting strategies, and modulation of EV biogenesis. Finally, key translational challenges-such as EV heterogeneity, biodistribution, immune clearance, and standardization-are discussed to define future directions for leveraging EVs as diagnostic and therapeutic platforms in AD.