Hemostasis components in cerebral amyloid angiopathy and Alzheimer's disease.

Abstract

Increased cerebrovascular amyloid-β (Aβ) deposition represents the main pathogenic mechanisms characterizing Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). Whereas an increasing number of studies define the contribution of fibrin(ogen) to neurodegeneration, how other hemostasis factors might be pleiotropically involved in the AD and CAA remains overlooked. Although traditionally regarded as pertaining to hemostasis, these proteins are also modulators of inflammation and angiogenesis, and exert cytoprotective functions. This review discusses the contribution of hemostasis components to Aβ cerebrovascular deposition, which settle the way to endothelial and blood-brain barrier dysfunction, vessel fragility, cerebral bleeding, and the associated cognitive changes. From the primary hemostasis, the process that refers to platelet aggregation, we discuss evidence regarding the von Willebrand factor (vWF) and its regulator ADAMTS13. Then, from the secondary hemostasis, we focus on tissue factor, which triggers the extrinsic coagulation cascade, andon the main inhibitors of coagulation, i.e., tissue factor pathway inhibitor (TFPI), and the components of protein C pathway. Last, from the tertiary hemostasis, we discuss evidence on FXIII, involved in fibrin cross-linking, and on components of fibrinolysis, including tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA) and its receptor uPA(R), and plasminogen activator inhibitor-1 (PAI-1). Increased knowledge on contributors of Aβ-related disease progression may favor new therapeutic approaches for early modifiable risk factors.