Pat Metharom

Investigating the effect of Factor Xa anticoagulant on dementia risk

Award: 
Dementia Australia Research Foundation – Norma Beaconsfield Project Grant
Status: 
In Progress
Project Snapshot: 

Individuals with an irregular heartbeat or recurrent blood clots are often prescribed drugs that thin the blood long-term. Some of these treatments include drugs inhibiting FXa, an important protein of the blood clotting process. However, FXa is known to be capable of performing multiple tasks besides regulating clots. In platelets, a type of blood cells that are important in wound healing and clot formation, FXa is capable of controlling ADAM10, a protein responsible for managing the breakdown of Amyloid Precursor Protein (APP) into harmless fragments. Reduced function of FXa may potentially cause incorrect processing of APP into Amyloid Beta (Aβ) peptides, a sticky toxic substance that drives the development of Alzheimer's disease. As platelets are the main producer of APP in the blood, we first aim to investigate, in test-tube settings, the processing of APP in healthy platelets after exposure to FXa inhibitors. Next, we will give anti-FXa drugs to mice, and then analyse their blood for signs associated with Aβ production. Finally, we will compare the blood of patients on long-term FXa inhibitor and other anticoagulants for levels of Aβ peptides. As direct FXa inhibitors are now widely used, we must understand how these drugs may increase the risk of dementia.