Figure 6.

Retromer Stabilization Decreases the pTAU/tTAU Ratio and Knockdown of Retromer Assembly Subunit VPS35 Increases pTAU/tTAU Ratio Independently of APP Expression in Human Neurons

(A) APP KO neurons were generated from APP^Dp cells by CRISPR/Cas9 genome editing have no detectable levels of Aβ peptides.

(B) APP KO neurons show a significant reduction in pTAU (Thr 231) after treatment with R33.

(C) tTAU levels are not affected in APP KO neurons after treatment with R33.

(D) The pTAU/tTAU ratio is significantly reduced in APP KO neurons after treatment with R33.

(E) APP KO neurons transduced with VPS35 shRNA show a significant increase in pTAU/tTAU ratio compared with scrambled shRNA (SCR shRNA).

n = 3 independent experiments per treatment/condition. For each comparison, a two-tailed t test was performed. ^∗∗p < 0.01, ^∗∗∗p < 0.001, ^∗∗∗∗p < 0.0001. NS, nonsignificant. Error bars represent SD. See also Figures S5 and S6.