PAR4 misexpression in the cerebrovasculature drives excess fibrin deposition in 5XFAD mouse and cognitive decline in AD patients

In a human study the PAR4 gene F2RL3 mRNA expression is associated with multiple AD-relevant outcomes and its encoded product, PAR4, may play a role in disease pathogenesis. PAR4 is a platelet receptor that functions upstream of fibrin deposition in 5xFAD amyloid mice, leading to misexpression in the microvasculature. Fibrin deposits have been reported to be inflammatory in 5xFAD and future work will focus on teasing apart the contribution of PAR4 mediated fibrin deposits in inflammation and microglial activation.