•Alzheimer’s Disease (AD) is characterized by amyloid and tau pathology, neuroinflammation, and blood-brain barrier (BBB) compromise.

•Fibrinogen (FIB), a plasma glycoprotein with roles in coagulation and inflammation, does not normally permeate the BBB.

•FIB can be observed diffusively extending into the brain from some vasculature in AD patients, correlating with disease severity.

•Previous studies have shown that FIB interacts directly with both amyloid and tau proteins, suggesting a link between vascular dysfunction and AD pathology accumulation.

•In this study, we assessed the spatial overlap between FIB, amyloid, and tau in the frontal cortex of post-mortem human AD patients.

 

In this small cohort study, we quantitatively analyzed the spatial relationships between fibrinogen, amyloid, and tau pathology within the frontal cortex of AD patients. While amyloid and tau were typically positively correlated in gray matter, their relationships with fibrinogen varied by APOE4 status. In gray matter, fibrinogen positively correlated with amyloid (non-carriers) or tau (carriers), but not both. In white matter, fibrinogen correlated positively with amyloid and negatively with tau in non-carriers, versus positively with tau in carriers.  APOE4 status appears to partially modify the relationship between these pathologies in both gray matter and white matter, which suggests larger cohort studies are warranted to examine the heterogeneity among AD patient populations.