Oligomeric amyloid-β induces early and widespread changes to the proteome in human iPSC-derived neurons

One of the most studied hallmarks of AD is the progressive propagation of Aβ pathology, thought to be caused by the spreading of oAβ among interconnected brain regions from neuron to neuron^5,22, further reviewed in^1,2,3,4. In this work, we aim to elucidate intracellular protein changes elicited by oAβ upon naïve human neurons, thereby furthering our understanding of the early mediators involved in Aβ-induced pathogenesis. To do this, we used well characterized iPSC-derived ltNES cells, which upon differentiation, are electrophysiologically mature and display mature neuronal markers^{14,15,16,17,18,19,20,21}. Since Aβ oligomers are thought to be the most relevant aggregates in AD pathology, we challenged the differentiated neurons with 1 µM oAβ over 24 h to mimic the early phase of oAβ challenge, similar to previous studies^{22,23,26,27,28,29,30}. Previous studies have shown…