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Figure 1. Analysis of proteome cargoes of tau-propagating EVs generated by neurons expressing familial mutant forms of tau and presenilin. EVs: extracellular vesicles. Tau-propagating EVs produced by human iPSC neurons expressing familial mutant tau P301L and V337 mutations of FTDP-17^[24], and mutant presenilin of A246E^[25] of Alzheimer’s disease were analyzed for (A) initiation of tau propagation in the rodent brain; (B) comparison of mutant EV proteome cargoes compared to wild-type control EVs; (C) comparison of mTau and mPS1 EVs proteomes that promote tau pathogenesis. The mTau iPSC neuronal cell line was obtained by lentivirus expression in a normal iPSC cell line, with a control consisting of expressing control lentivirus without the mutant Tau construct^[24]. The mPS1 iPSC neuronal cell line was generated by reprogramming from a biopsy from a patient harboring the mPS1, and the control wild-type PS1 iPSC cell line was generated by reprogramming from a biopsy from a normal healthy patient having wild-type PS1^[25]. It is noted that the mTau and mPS1 iPSC neurons are generated from different human patient biopsies and, therefore, possess different genetic backgrounds. The study of human iPSCs from different genetic backgrounds is logical to gain an understanding of tauopathies that afflict various human populations (The BioRender resource was used for the preparation of Figure 1).