Figure 4.

Enhanced BACE1 and β-secretase processing of APP in p25 Tg mice. a, Increased BACE1 expression was shown by immunoblot analysis of RIPA-soluble forebrain extracts from 2 week induced CK–p25 mice. Data are mean ± SEM values for WT (n = 3) and CK-p25 Tg (n = 3) mice. BACE1 levels were not increased in uninduced p25 Tg mice (data not shown). b, Increased generation of APP C-terminal fragments C89 and C99 in CK–p25 and PD-APP/CK–p25 mice compared with their respective controls. Blots are representative from mice induced for 5–8 weeks. c, Densitometric analysis of C-terminal fragment bands plotted relative to WT (top) or PD-APP (bottom) C99 intensities. Data are mean ± SEM values; n = 3 for each genotype. *Statistically different C99 or C89 immunoreactivity by two-tailed, unpaired Student's t test from WT or PD-APP (top, p = 0.027 for C99 and p = 0.020 for C89; and bottom, p = 0.028 for C99 and p = 0.053 for C89). d, Increased BACE1 expression as shown by immunohistochemical analyses. Shown is a representative image from the cortex of a 2 week induced CK–p25 mouse. e, BACE1 and C-terminal APP fragments are concomitantly increased at 5 weeks of induction. DAPI, 4′,6′-Diamidino-2-phenylindole; CTF, C-terminal fragments.