Pharmacologic blockade of 5LO decreases Aβ peptides levels and deposition in the 3×Tg mice via the γ-secretase pathway.

A, B. RIPA-soluble (RIPA) and formic acid extractable (FA) Aβ1-40 and Aβ1-42 levels in cortex of 3×Tg receiving zileuton or vehicle were measured by sandwich ELISA. (n = 9 for control, and n = 9 for zileuton; *p<0.05). C. Representative sections of brains from 3×Tg mice receiving zileuton or placebo (control) immunostained with 4G8 antibody. D. Quantification of the area occupied by Aβ immunoreactivity in brain of 3×Tg mice receiving zileuton or placebo (n = 3 control, and n = 3 zileuton; *p<0.05). E. Representative western blots of APP, ADAM-10, BACE-1, sAPPs, CTFs, PS1, Nicastrin, Pen-2, and APH-1 in the cortex of 3×Tg mice receiving zileuton or vehicle. F. Densitometric analyses of the immunoreactivities to the antibodies shown in the previous panel. (n = 4, *p<0.05). Values represent mean ± SEM.