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. 2016 Sep 29;291(46):24041–24053. doi: 10.1074/jbc.M116.744722

FIGURE 1.

FIGURE 1.

Amino acid sequence of the human and mouse Aβ region and secretase cleavage sites, and generation of various forms of Aβ in cells overexpressing human or mouse APP. A, amino acid sequence of the human and mouse Aβ regions. Cleavage sites of α-secretase (α-site), β-secretase (BACE1; β- and β′-sites), and γ-secretase (γ-sites) to generate Aβ(XX-40) and Aβ(XX-42) are indicated by arrows. Numbering is for the APP-(770) isoform. Amino acid substitutions observed in FAD mutations are underlined. Mouse Aβ differs from human Aβ at three positions, indicated by a gray background. Aβ(1–40) and Aβ(11–40) are indicated by lines. B, representative MS spectra of Aβ species secreted from human and mouse cells expressing either hAPP or mAPP. Aβ forms generated from human and mouse APP expressed in mouse N2a and human SHSY5Y neuroblastoma cells were analyzed by MALDI-MS/MS analysis. Aβ(1-XX) is the product of cleavage at the β-site, whereas Aβ(11-XX) is the product of cleavage at the β′-site. C, levels of Aβ(11-XX) production from each APP in cells. Aβ(11–40)/Aβ(1–40) ratios from human and mouse APP in N2a and SHSY5Y cells were compared (left), along with the Aβ(11–34)/Aβ(1–34) ratio from hAPP and mAPP in N2a cells (right). Data are shown as mean ± S.E. Statistical significance was examined by Student's t test (n = 3), and p values are indicated (*, p < 0.05; ****, p < 0.0001).