Kapogiannis D, et al. - By analyzing longitudinal samples from Baltimore Longitudinal Study of Aging (BLSA) candidates, researchers sought to validate neuronal-enriched extracellular vesicle (nEV) biomarkers for Alzheimer disease (AD) prediction. In total, 887 longitudinal plasma samples were analyzed from 128 BLSA participants who eventually developed AD and 222 age and sex-matched controls that stayed cognitively normal. Investigators found that combining extracellular vesicle biomarkers anticipated AD with high discernment accuracy and specificity approximately four years prior to symptom onset. Cognitive performance was linked to preclinical levels of nEV biomarkers. In a case-control cohort from Johns Hopkins, biomarkers were further validated. These results should motivate developing nEV biomarkers towards a clinical blood test for AD.