fig4

Figure 4. NDEVs and their source plasma samples were used to measure BDNF and proBDNF in early AD and control donors. (A) Measurements in the BioIVT cohort showed high enrichment of proBDNF levels in NDEVs (P < 0.001) compared to unprocessed plasma. Moreover, we observed lower levels of NDEVs-associated proBDNF in early AD compared to control individuals (P = 0.002), while no difference was observed in unprocessed plasma. (B) BDNF was 2.6-fold lower in NDEVs than in plasma (P < 0.01) and did not vary between AD and controls. (C) ProBDNF measurements in two independently stored aliquots from 20 samples showed a moderately strong correlation (R² =0.7, P < 0.0001). (D, E) NDEVs-associated proBDNF was measured in two additional cohorts from NIA and PMED; the decrease in NDEVs-associated proBDNF in early AD compared to control individuals was reproduced in the NIA cohort (P = 0.001), while the PMED cohort generated a similar trend that did not reach statistical significance (P = 0.09), potentially due to an insufficient number of control samples.