Aβ interacts with the α-chain of fibrinogen, producing a plasmin-resistant fibrin fragment during fibrinolysis. (A) Fibrin was digested with plasmin in the presence or absence of Aβ42. A plasmin-resistant fragment was observed only in the presence of Aβ42 (arrow). The same experiment was done without thrombin. In the absence of thrombin, plasmin degradation-resistant PRFF was also observed in the presence of Aβ42. Images are representative of ≥3 experiments. (B) Mass spectrometry analysis of the fragments in panels A and C showed they were derived from the α-chain of fibrinogen. Green residues were identified by N-terminal sequencing of band in panel A, red residues were identified by mass spectrometry analysis of band in panel A, and underlined residues were identified by mass spectrometry analysis of band in panel C. (C) Fibrinogen was partially digested with plasmin, incubated with biotinylated Aβ42, and Aβ42 was pulled down with streptavidin (SA)-coated beads. A fibrinogen fragment that bound to Aβ was observed (top arrow).