FIGURE 3.

Alternative cleavage of human and mouse APP by β-secretase. A, representative MS spectra of Aβ with amino-terminal β- and β′-cleavage sites generated from hAPP (with or without amino acid substitutions found in the mouse protein) and mAPP. Spectra of Aβ species from hAPP (a, WT), hAPP R676G (b), hAPP Y681F (c), hAPP H684R (d), hAPP R676G/Y681F/H684R (e, 3mut), and innate mAPP (f, WT) expressed in N2a cells were analyzed by IP-MS. B, levels of Aβ(11-XX) production from each APP are indicated as the Aβ(11–40)/Aβ(1–40) ratio. Data are shown as mean ± S.E. Statistical significance to WT was examined by Dunnett's multiple comparisons test (n = 5), and p values are indicated (***, p < 0.001).