Coagulation factor XIIIa cross-links amyloid β into dimers and oligomers and to blood proteins. J Biol Chem 2019 Jan 11;294(2):390-396
Date
11/10/2018Pubmed ID
30409906Pubmed Central ID
PMC6333891DOI
10.1074/jbc.RA118.005352Scopus ID
2-s2.0-85059908563 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
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 (kcat/Km = 1.5 × 105 m-1s-1), as well as to fibrin, platelet proteins, and blood clots under flow in vitro Aβ40 also increased the stiffness of platelet-rich plasma clots in the presence of FXIIIa. These results suggest that FXIIIa-mediated cross-linking may contribute to the formation of Aβ deposits in CAA and Alzheimer's disease.
Author List
Hur WS, Mazinani N, Lu XJD, Yefet LS, Byrnes JR, Ho L, Yeon JH, Filipenko S, Wolberg AS, Jefferies WA, Kastrup CJAuthor
Christian Kastrup PhD Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Alzheimer DiseaseAmyloid beta-Peptides
Blood Platelets
Blood Proteins
Cerebral Amyloid Angiopathy
Factor XIIIa
Fibrin
Humans
Peptide Fragments
Platelet-Rich Plasma
Protein Aggregation, Pathological
Protein Multimerization