Figure 2.

TO901317 reduces Aβ burden in the APP23 transgenic mouse model of AD. A, B, Concentrations of human Aβ40 and Aβ42 in formic acid extracts (A) or soluble fraction (B) in APP23 mice, as determined by sandwich ELISA, were strongly reduced in response to TO901317 (TO; 50 mg/kg per day for 7 weeks). 6E10 was used as a capture antibody and anti-Aβ40 as detection antibody. C, Sandwich immunoassay on Triton X-100 extracts or Western blot determination on brain homogenates showed a minor but significant reduction of APP and sAPPα upon TO901317 treatment. Capture antibodies in the sandwich immunoassay were anti-sAPPα and anti-sAPPβ; reporter was anti-APP. For Western blot, detection of APP and the C-terminal fragments 6E10 was used. D, Endogenous Aβ levels remained unaffected by drug treatment as demonstrated by ECL immunoassay. E, Representative micrographs of Aβ immunohistochemistry with antibody 2964, showing the frontal cortex (Cx) or subiculum (Sb) of TO901317- and vehicle-treated APP23 mice. Asterisks indicate significant differences (unpaired Student's t test, *p < 0.05, n = 12). Data represent means ± SEM. F, Thioflavin S-positive area is reduced in brain sections of APP23 mice treated with TO901317. Scale bars, 200 μm. WT, Wild type.