Composition and activity of the proteasome in human iPSC-derived neuronal model of early-stage sporadic Alzheimer's disease

Introduction The proteasome is a critical cellular degradative machinery impaired in late-stage Alzheimer's disease (AD). However, the status and activity of the proteasome in early-stage sporadic AD (sAD) is unknown. Methods A cellular model of human early-stage sAD was generated from sAD patient iPSC-derived cortical neurons by dual-SMAD inhibition. The iPSCs, neuroprogenitors, and cortical neurons were validated by the expressions of key markers. The level of total intraneuronal A{beta} was measured by ELISA. Composition and native proteolytic activities of the proteasome in control and sAD cortical neurons were measured using complementary fluorogenic probes. Results Control and sAD pati