Amyloid precursor protein is required for in vitro platelet adhesion to amyloid peptides and potentiation of thrombus formation.

Cellular Signalling
Caterina VisconteIlaria Canobbio

Abstract

Amyloid precursor protein (APP) is the precursor of amyloid β (Aβ) peptides, whose accumulation in the brain is associated with Alzheimer's disease. APP is also expressed on the platelet surface and Aβ peptides are platelet agonists. The physiological role of APP is largely unknown. In neurons, APP acts as an adhesive receptor, facilitating integrin-mediated cell adhesion, while in platelets it regulates coagulation and venous thrombosis. In this work, we analyzed platelets from APP KO mice to investigate whether membrane APP supports platelet adhesion to physiological and pathological substrates. We found that APP-null platelets adhered and spread normally on collagen, von Willebrand Factor or fibrinogen. However, adhesion on immobilized Aβ peptides Aβ1-40, Aβ1-42 and Aβ25-35 was completely abolished in platelets lacking APP. By contrast, platelet activation and aggregation induced by Aβ peptides occurred normally in the absence of APP. Adhesion of APP-transfected HEK293 to Aβ peptides was significantly higher than that of control cells expressing low levels of APP. Co-coating of Aβ1-42 and Aβ25-35 with collagen strongly potentiated platelet adhesion when whole blood from wild type mice was perfused at arterial shear rate, but...Continue Reading

Citations

Aug 14, 2020·Journal of Thrombosis and Haemostasis : JTH·Caterina VisconteIlaria Canobbio
May 21, 2020·Frontiers in Immunology·Odette Leiter, Tara L Walker
Apr 23, 2019·Oxidative Medicine and Cellular Longevity·Aisha Alsheikh AbubakerGiordano Pula
Nov 26, 2020·International Journal of Molecular Sciences·Benedetta IzziAlessandro Gialluisi
Dec 23, 2020·International Journal of Molecular Sciences·Giulia GagnoAneta Aleksova
Oct 31, 2020·Frontiers in Immunology·Elias RawishHarald F Langer
Apr 26, 2021·Pediatric Research·Hanna DanielssonAnn Hellström

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