Biomarkers.

Area of Science:

• Neuroscience
• Biomarker Development
• Medical Imaging

Background:

• Alzheimer's disease (AD) is the most common dementia, characterized by complex neuropathology.
• A prothrombotic state, leading to fibrin accumulation in cerebral vessels, is implicated in AD pathogenesis.
• Fibrin deposition exacerbates hypoperfusion, neurodegeneration, and blood-brain barrier disruption in a subset of AD patients.

Purpose of the Study:

• To develop novel imaging biomarkers for non-invasively detecting the pro-coagulant state in AD.
• To utilize fibrin-binding probes (FBPs) for identifying cerebral fibrin accumulation.
• To establish early detection methods for identifying AD patients who may benefit from anticoagulant therapies.

Main Methods:

• The BioClotAD project employs in vitro, ex vivo, and in vivo assays across multiple European sites.
• Fibrin-binding probes (FBPs) are tested for in vivo detection of cerebral occlusions via nuclear imaging.
• FBPs coupled with a transferrin receptor antibody (FBP-TfR) are developed to enhance blood-brain barrier penetration for optical and nuclear imaging, with validation in human AD brain samples.

Main Results:

• Feasible neuroimaging strategies were developed to detect and localize fibrin accumulation in vivo in AD models.
• The study identified specific regional distributions of cerebral fibrin deposition.
• These findings lay the groundwork for future clinical trials investigating neuroimaging of fibrin in AD.

Conclusions:

• The developed neuroimaging biomarkers enable early detection of the pro-thrombotic state in AD.
• This early detection opens opportunities for personalized anticoagulant therapies to potentially delay disease progression.
• The BioClotAD project paves the way for advancing diagnostic and therapeutic approaches in Alzheimer's disease.