Fig. 5: Schematic model showing APP695WT vs APP695E590D in AD pathogenesis.
From: APP E590D mutation increases generation of Aβ and Aη peptides and exacerbates tauopathy
APP695E590D increases η-processing of APP on the cell surface (i.e., presynaptic), resulting in elevated Aη generation. APP695E590D also increases APP internalization, promoting Aβ generation through β-secretase processing (BACE1). The combination of Aη, Aβ, and/or APP695E590D ectodomain drives tau seeding and aggregation, contributing to synaptic dysfunction (i.e,. postsynaptic).
