Kapogiannis D, Mustapic M, Shardell MD, et al. - Researchers examined the value of plasma neuronal-enriched extracellular vesicles (nEVs) in diagnosing Alzheimer disease (AD) at the preclinical and clinical stages. In this case-control study, they included 887 longitudinal plasma samples (split into training and test sets) from cognitively normal participants in the Baltimore Longitudinal Study of Aging cohort who developed AD up to January 2015 and age- and sex-matched controls who remained cognitively normal over a similar length of follow-up. About 4 years before symptom onset, Alzheimer disease could be predicted via combining extracellular vesicle biomarkers with high discrimination accuracy and specificity; individual biomarkers were associated with cognitive performance. In a case-control cohort from Johns Hopkins, further validation of the biomarkers was done. Findings justify further development of nEV biomarkers toward a clinical blood test for AD.