Figure 2.

Sublethal stretch increases extracellular Aβ generation in human neurons. A, Quantitative analysis of extracellular Aβ40 and Aβ42 and resultant Aβ42/Aβ40 ratio, measured in neuronal media collected 24 h after stretch. Neuronal cultures were washed with PBS, and fresh media was added before stretch was imposed (*p = 0.0418 for Aβ40; *p = 0.0278 for Aβ42) (n = 7). Quantification of extracellular Aβ levels 24 h after stretch in neurons stretched in the presence of (B) βsi-IV (4 μm) (***p = 0.0005 for Aβ40; **p = 0.0040 for Aβ42) (n = 9) or (C) CE (200 nm) (*p = 0.0493 for Aβ40; *p = 0.0041 for Aβ42). Data are percent of change in extracellular Aβ levels after stretch relative to extracellular Aβ levels before stretch (n = 6) (vehicle = DMSO 0.001%). D, Diagram showing experimental design used to measure stretch effects on Aβ generation after CE reversible inhibition and quantitative analysis of extracellular Aβ40 and Aβ42 levels 24 h after stretch in neurons previously exposed to CE (200 nm) during 16 h (**p = 0.0035 for Aβ40; **p = 0.0042 for Aβ42) (n = 13). Measurements of intracellular Aβ levels after stretch are displayed in Extended Data Figure 2-1. Data are mean ± SEM; means were compared by unpaired Student's t test.