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

Caterina Visconte, Jessica Canino, Gianni Francesco Guidetti, Marta Zarà, Claudio Seppi, Aisha Alsheikh Abubaker, Giordano Pula, Mauro Torti, Ilaria Canobbio

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

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 languageEnglish
Pages (from-to)95-102
Number of pages8
JournalCellular Signalling
Volume52
Early online date30 Aug 2018
DOIs
Publication statusPublished - 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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