Unveiling the procoagulant state in Alzheimer's disease: A novel PET imaging strategy

INTRODUCTION: A subset of Alzheimer's disease (AD) patients exhibits a procoagulant state that remains undiagnosed despite available treatments. We developed positron emission tomography (PET) strategies to in vivo detect cerebral microthrombi in TgCRND8 mice. METHODS: PET was performed with a fibrin-binding probe (FBP) in TgCRND8 and wild-type mice using a zirconium-89-radiolabeled and a click-chemistry pre-targeted gallium-68 radiotracer. Platelet content was assessed in post mortem brain tissue from AD patients and TgCRND8 mice, and evaluated by PET using a CD41 pre-targeted gallium-68 nanoradiotracer. RESULTS: Cerebral FBP uptake differentiated TgCRND8 from wild-type mice, particularly ex vivo and with advancing age. Cerebral fibrin burden correlated with platelet content in AD patients, and elevated cerebral platelet burden in TgCRND8 mice was confirmed in post mortem tissue and in vivo by PET. DISCUSSION: Our findings support PET-based detection of AD-associated cerebral microthrombi and the development of imaging biomarkers to stratify AD patients by procoagulant status and inform personalized therapies.