Figure 6.

APP Icelandic variant abrogates stretch-induced increase in Aβ generation. A, Sequencing of genome-edited single-cell derived hiPSC lines confirms the generation of isogenic hiPSC line carrying the APP Icelandic mutation in heterozygosis. B, Quantitative analysis of extracellular Aβ40, Aβ42, and resultant Aβ42/Aβ40 ratio, accumulated over 7 d of culture in APP^WT/Ice neurons compared with APP^WT/WT neurons. Aβ levels are shown as relative to total tau levels in matched cell lysates (**p = 0.0048 for Aβ40; **p = 0.0033 for Aβ42) (n = 9). C, Schematic diagram illustrating the experimental design used for the quantification of extracellular Aβ levels in APP^WT/Ice and APP^WT/WT neurons 24 h after stretch (APP^WT/WT, *p = 0.0418 for Aβ40; and *p = 0.0278 for Aβ42) (n = 7 or more). Exposure to GGPP increases Aβ generation in APP^WT/Ice neurons (Extended Data Fig. 6-1). D, Quantitative analysis of the APP^Ice-GFP movement parameters in axons immediately after stretch (n = 5). Data are presented relative to pre-stretch condition. Data are mean ± SEM; means were compared by unpaired Student's t test. Scale D, 10 µm.