Extended Data Fig. 4: Quantitative proteomic analysis of human tNeurons identifies proteins and pathways associated with aging and sAD.

(a) Heatmap of the differentially expressed proteins across tNeurons from young, aged, aged/sAD and fAD-PSEN1 donors. (b) Top-ranked proteins (rows) changing with aging and sAD (columns) based on log2-fold change (log2-FC). (c) Gene ontology (GO) analysis of the differentially expressed proteins between young, aged and aged/sAD tNeurons. Circle sizes reflect the number of proteins. (d) Network analysis of tNeuron proteomes, including proteins in the top-ranked pathways associated with young and sAD, revealed by GeneMANIA and GO. Comparison between healthy young (n = 3 individuals) and aged/sAD tNeurons (n = 6 individuals) at PID 40. Coloured circles represent the enrichment of identified proteins revealing by log2-FC: increase in red and decrease in blue. (e) Venn diagram reveals an overlap of differentially expressed proteins between tNeurons from aged and young donors, and between tNeurons from aged/sAD and young donors. The shared hits and assigned GO terms are showed in light green colour. Interaction network for the shared hits that are either increased or decreased in aged and aged/sAD tNeurons as compared with young tNeurons. Each node representing a single protein that is divided to reflect the individual change for aged vs. young (left) and aged/sAD vs. young (right). Protein abundance increases are shown in red, and decreases shown in blue.