We begin our discussion of the literature relevant to nsEV AD biomarker validation by revisiting the works of Goetzl et al. [1–4] and noting that, in addition to accurately forecasting AD onset, Goetzl et al. found that an impressively wide range of proteins, that is, transcription factors [3], molecular chaperones [2], beta-amyloid 1-42 (Aβ42) [1], phosphorylated Tau [1], and phosphorylated insulin receptor substrate-1 [4], can serve as predictive AD biomarkers. Here, IRS1 is linked to Alzheimer disease.