Development of a neuroimaging biomarker to identify the pro-coagulant state in Alzheimer’s disease

Alzheimer’s disease (AD) is a multifactorial disorder characterized by amyloid plaques, tau tangles and neurodegeneration. One important process contributing to pathology is the so-called pro-coagulant state.

A decrease in cerebral blood flow promotes a pro-thrombotic milieu in the AD brain, favoring formation of fibrin clots, which contribute to neurodegeneration.

Interestingly, long-term treatment with thrombin inhibitors prevents the deposition of cerebral fibrin and preserves cognition in AD mice. This pro-coagulant state is not present in all AD patients.

Therefore, patients that would benefit from anticoagulant treatment need to be carefully identified.The present joint proposal aims to develop a non-invasive imaging biomarker to identify the pro-coagulant state in AD.

The research consortium comprises experts in neuroscience, biochemistry, preclinical imaging, radiochemistry and translational approaches from cutting-edge European institutions.

By combining molecular biology approaches with molecular imaging tools, we will develop an imaging probe to detect fibrin clots in vessels and in AD brain parenchyma.

Such a probe will be an instrumental biomarker to 1) better pre-select AD patients with a pro-coagulant state, suitable for treatment with anti-thrombotics; and 2) avoid the exposure of AD patients with no pro-thrombotic state to anticoagulants.

Despite a relatively low risk of intracranial bleedings, treatment should be carefully evaluated on an individual basis.