Figure 2. The FXII-FVII pathway detects and degrades Aβ40.

(A–J) Changes in plasma coagulation factors in male C57BL/6 mice treated with EP and/or Aβ40. Mice were treated with vehicle or EP (0.5 mg/kg) i.p. once daily for 5 days, and 1 h after the final treatment, the mice were injected i.p. with vehicle or Aβ40 (40 μg/kg). Blood samples were obtained from the mice at 6 h after Aβ40/vehicle treatment; 7.5 μl plasma per sample was analyzed by Western blotting. Arrows indicate the cleaved fragments of the coagulation factors. Plasma levels of FI and Aβ were measured by ELISA. Error bars in I and J indicate SD (n = 3); ^****P < 0.0001. (K) Aβ40 (0, 0.05 and 0.5 µM) was incubated with FXII (0.97 nM) in ZnCl₂-containing PBS at RT; FXII activation was measured by a chromogenic assay. Each value is mean ± SD (n = 3). (L) Aβ40 (2.2 µM) was incubated alone or with FVIIa (10 nM) plus TF (10 nM) in CaCl₂-containing PBS at RT for indicated times, and an equal volume of each incubation was separated by SDS-PAGE and stained by silver. FVIIa and TF were incubated without Aβ40, as a control.