L1CAM and Alzheimer disease: Shi et al. (2014) and Fiandaca et al. (2015) independently established an immunoaffinity capturing protocol to isolate L1CAM-containing EVs (referred to as NDEs) from plasma. L1CAM is a cell adhesion molecule highly expressed in neurons. Two years later, Goetzl et al. (2016b) made progress in ADEs using mouse anti-human GLAST biotinylated antibodies. The study examined the association between cargo proteins of plasma ADEs and AD pathology. The first clinical study on ODEs was published in 2019 (Ohmichi et al., 2019).