Coagulation factor XIIIa cross-links amyloid β into dimers and oligomers and to blood proteins.

ABSTRACT: In cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD), the amyloid β (Aβ) peptide deposits along the vascular lumen, leading to degeneration and dysfunction of surrounding tissues. Activated coagulation factor XIIIa (FXIIIa) covalently cross-links proteins in blood and vasculature, such as in blood clots and on the extracellular matrix. Although FXIIIa co-localizes with Aβ in CAA, the ability of FXIIIa to cross-link Aβ has not been demonstrated. Using Western blotting, kinetic assays, and microfluidic analyses, we show that FXIIIa covalently cross-links Aβ40 into dimers and oligomers (k_cat/K_m = 1.5 × 10⁵ m^-1s^-1), as well as to fibrin, platelet proteins, and blood clots under flow in vitro Aβ40 also incr

SUBMITTER: Hur WS 

PROVIDER: S-EPMC6333891 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature