Alzheimer's disease and vascular biology – A focus on the procoagulant state

Abstract

Alzheimer's disease (AD) is characterized by a multifactorial pathophysiology. Beyond its classical hallmarks, growing evidence highlights vascular contributions, including hemostatic dysregulation and a prothrombotic state in AD. This review focuses on recent findings concerning two key blood clot components–fibrin(ogen) and platelets–and their roles in AD pathology, including fibrinogen's abnormal accumulation in the AD brain, its interaction with amyloid-β, together with the associated impacts on clot stability, vascular occlusion, and neuroinflammation; and the potential switch of platelets along the AD continuum from protective to deleterious. This review provides an update on the interplay between vascular dysfunction and AD, underscoring the need for comprehensive integrative research to address AD's complexity and advocating for personalized approaches to tackle this multifaceted disorder.