Amyloid-beta-fibrinogen complex (Aβ-Fbg)

The Amyloid-beta-fibrinogen complex is a pathological protein-protein interaction that plays a critical role in the neurovascular dysfunction associated with Alzheimer's disease (AD) [1.2.1, 1.5.1]. Amyloid-beta (Aβ), particularly the Aβ42 isoform, binds specifically to fibrinogen at the C-terminus of the fibrinogen β-chain and the αC region, inducing structural changes that result in the formation of abnormal, plasmin-resistant fibrin clots [1.2.2, 1.4.1]. These persistent clots lead to reduced cerebral blood flow, chronic neuroinflammation, and blood-brain barrier disruption, which collectively accelerate neurodegeneration [1.1.1, 1.3.1]. Studies have shown that the Aβ-fibrinogen complex is synergistically toxic, promoting greater synaptic loss and tau phosphorylation than either protein individually [1.2.3, 1.5.3]. Therapeutic strategies, including the small molecule RU-505, aim to selectively disrupt this interaction to restore normal fibrinolysis and alleviate cognitive impairment [1.3.1, 1.3.4]. By targeting this specific interface, researchers hope to treat the vascular components of Alzheimer's without affecting systemic blood clotting mechanisms [1.3.5, 1.5.2].

Other names

Amyloid-beta-fibrinogen interactionAβ-fibrinogen complexFibrinogen-amyloid beta complexAβ-Fbg interactionAmyloid-beta at the fibrinogen-binding interface

Selective inhibition of the protein-protein interaction between amyloid-beta and fibrinogen to restore normal fibrin clot structure and promote fibrinolysis.