Neuron-derived extracellular vesicles carrying specific microRNA signatures emerge as potentially transformative biomarkers for Alzheimer's disease, capturing brain pathology changes before clinical symptoms appear. These circulating vesicles, released by dying neurons, contain molecular cargo that reflects amyloid and tau accumulation with greater sensitivity than traditional plasma proteins like p-tau217 or GFAP. The vesicular approach addresses a critical gap in early detection, as current blood tests often miss preclinical stages when interventions might be most effective. This represents a significant evolution beyond the established AT(N) framework that relies on amyloid, tau, and neurodegeneration markers. The vesicle-based signatures could revolutionize population screening by providing accessible, scalable testing that doesn't require expensive PET scans or invasive spinal taps. However, the technology faces substantial validation hurdles. Current datasets remain small and largely confined to research cohorts, while standardized collection and processing protocols are still under development. The microRNA panels also require external validation across diverse populations before clinical deployment. Despite these limitations, the biological rationale is compelling—these vesicles essentially function as liquid biopsies of the brain, potentially enabling detection years before cognitive decline becomes apparent.