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A key molecular hallmark of ADNPC is the accumulation of amyloid\u2010\u03b2 plaques. \u03b2\u2010secretase plays a critical role in the upstream pathological cleavage of amyloid precursor protein (APP), producing amyloid\u2010\u03b2 peptides that are prone to misfolding, ultimately contributing to plaque formation. Neuronal extracellular vesicles (NEVs) in the blood transport \u03b2\u2010secretase and preserve its activity, allowing for noninvasive profiling of \u03b2\u2010secretase activity for detecting early onset of ADNPC. In this study, a novel approach is approached for noninvasive assessment of \u03b2\u2010secretase activity in AD patients using an NEV \u03b2\u2010secretase activity assay. This assay identifies NEVs exhibiting colocalization of NEV markers with AD\u2010associated \u03b2\u2010secretase, generating a \u03b2\u2010secretase activity profile for each patient. 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