Figure 13.

TF2D-5a inhibits tau aggregation in cells. In order to compare the abiliy of TF2D-5a and CP-1 to inhibit tau aggregation without interference from potentially different cell permeabilities, we used lipofectamine for cell transfection, as described in the Section 4. (A) TF2D-5a and the negative-control D-peptide CP-1 were tested for their ability to inhibit tau aggregation in tauK18(LM)-YFP cells. “ns” abbreviates the expression “non significant”. (B) In contrast to unseeded cells, which did not harbor any tau aggregates at day three after plating, seeding with sonicated tau fibrils induced aggregation in approximately 40% of cells after three days of incubation. (D) A three-day treatment with the negative-control D-peptide CP-1 did not inhibit tau aggregation. (F) In contrast, treatment with increasing concentrations of TF2D-5a led to a concentration-dependent reduction in the number of cells with tau aggregates, which was significant at 12.5 µM and further reduced tau aggregation at 25 µM and 50 µM TF2D-5a. Panels (C,E,G) represent magnifications of cells indicated by white rectangles in panels (B,D,F), respectively. The scale bar represents 50 µm for panels (B,D,F), and 5 µm for panels (C,E,G). Significance was calculated using one-way ANOVA followed by Dunnett’s multiple comparisons test. Three asterisks denote a p value less than 0.001 and four asterisks a p value less than 0.0001.