Unveiling the Procoagulant State in Alzheimer’s Disease

Alzheimer’s Disease (AD) is a progressive neurodegenerative dementia characterized by a complex, multifactorial pathology. Beyond the well-known accumulation of amyloid-β (A) and Tau deposits, increasing evidence underscores a significant but largely overlooked vascular component in the brain of these patients. In this seminar, I will explore the procoagulant state in AD—a phenomenon where Aβ interacts with blood components (fibrinogen and platelets) to form abnormal, degradation-resistant clots. These persistent microthrombi act as "roadblocks" in the cerebral vasculature, reducing blood flow. This chronic hypoperfusion accelerates neurodegeneration and, ultimately, cognitive decline.

Fortunately, recent research has shown that targeting the coagulation cascade can effectively reduce these deleterious consequences. However, because not all patients are affected by this procoagulant milieu, the great challenge lies in identifying who would benefit from these therapies through early patient stratification. I will present our laboratory's recent breakthroughs in neuroimaging, where we have developed the first strategies to detect these tiny clots in the living brain of AD models. By utilizing Nobel Prize-winning "click chemistry” technology and PET scans, we are moving from post-mortem confirmation to in vivo detection. Altogether, our research aims to demonstrate how targeting the vascular-coagulation axis can serve as a novel strategy to enable safer, more effective, and personalized therapies in AD.

Speaker: Marta Casquero Veiga. Postdoctoral Fellow. Laboratorio de Investigación Neurovascular en la Enfermedad de Alzheimer (LINEAlz). Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, Spain). Centro Nacional de Investigaciones Cardiovasculares (CNIC, Spain).