Tau–Amyloid precursor protein (APP) protein–protein interaction interface (Tau–APP PPI interface)

The Tau–Amyloid precursor protein (APP) protein–protein interaction interface is a pathological junction where two primary proteins associated with Alzheimer's disease, Tau and APP, physically associate [1, 2]. Tau is a microtubule-associated protein that stabilizes axons, while APP is a transmembrane protein whose proteolytic cleavage generates amyloid-beta (Aβ) peptides [3, 4]. Research suggests that the direct binding of Tau to APP facilitates the co-aggregation of these proteins, promoting the formation of neurotoxic plaques and tangles [2, 5]. This interface has emerged as a therapeutic target because disrupting the PPI can potentially reduce both Aβ and Tau pathologies simultaneously [2, 6]. Experimental inhibitors, such as the APP1-Tau1 peptide mixture and linked 'Flex' or 'Rigid' peptides, have shown efficacy in reducing amyloid burden and restoring cognitive function in animal models [2, 5]. Additionally, monoclonal antibodies like TNT1 target specific Tau domains involved in these interactions to prevent toxic signaling [7]. Targeting the interface aims to selectively block pathological synergy while preserving the essential physiological roles of the individual proteins [2, 8].

Other names

APP-Tau interaction interfaceTau-APP binding siteAmyloid precursor protein-Tau protein-protein interactionAPP-Tau PPI

Inhibition of the physical association between Tau and Amyloid Precursor Protein (APP) to prevent synergistic aggregation and neurotoxicity.