Apolipoprotein E4 – Amyloid-beta binding interface (ApoE4–Aβ interface)

The Apolipoprotein E4 (ApoE4) – Amyloid-beta (Aβ) binding interface is a pivotal molecular target in the study and treatment of Alzheimer's disease (AD). ApoE4 is recognized as the most significant genetic risk factor for late-onset AD, largely due to its role in modulating Aβ metabolism (Liu et al., 2013, Nature Reviews Neurology). The physical interaction between ApoE4 and Aβ peptides facilitates the nucleation and aggregation of Aβ into neurotoxic plaques while simultaneously hindering its clearance across the blood-brain barrier (Wisniewski & Drummond, 2020, Frontiers in Aging Neuroscience). This interface primarily involves the residues 12–28 of the Aβ peptide and specific regions within the ApoE protein (Pankiewicz et al., 2014, Journal of Alzheimer's Disease). Therapeutic interventions targeting this site, such as small molecules or decoy peptides like Aβ12–28P, aim to disrupt the formation of the ApoE/Aβ complex to reduce amyloid burden (Wisniewski & Goñi, 2014, Neuron). Unlike global ApoE inhibitors, targeting the specific binding interface seeks to preserve the essential lipid-transport functions of the protein while mitigating its pathological effects on amyloid pathology.

Other names

ApoE4-Aβ interaction siteApolipoprotein E4 - Amyloid beta peptide complexApoE-Aβ binding domainApoE4-Abeta interface

Inhibition of the physical binding between Apolipoprotein E4 and Amyloid-beta peptides to prevent the stabilization of amyloid seeds and enhance the clearance of Aβ monomers and oligomers.