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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 had no effects with blood from APP KO mice. These results demonstrate that APP selectively mediates platelet adhesion to Aβ under static condition but not platelet aggregation, and is responsible for Aβ-promoted potentiation of thrombus formation under flow. Therefore, APP may facilitate an early step in thrombus formation when Aβ peptides accumulate in cerebral vessel walls or atherosclerotic plaques.
Original language | English |
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Pages (from-to) | 95-102 |
Number of pages | 8 |
Journal | Cellular Signalling |
Volume | 52 |
Early online date | 30 Aug 2018 |
DOIs | |
Publication status | Published - 1 Dec 2018 |
Keywords
- Amyloid precursor protein
- Aβ peptides
- Platelet activation
- Platelet adhesion
- Thrombus formation
ASJC Scopus subject areas
- Cell Biology
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Characterisation of the Role of NADPH Oxidase 1 in Collagen-Dependent Activiation of Platelets: A Potential Target for the Development of Novel Antithrombotics
Pula, G. (PI) & Caggiano, L. (CoI)
1/12/15 → 30/11/18
Project: UK charity