Fig. 1. Global effects of intracellular Aβ on the transcriptome, proteome and metabolome of MC65 nerve cells.

a Aβ aggregation in induced (+Aβ) MC65 nerve cells was confirmed by Western blotting at days 0, 1 and 2 and compared to non-induced (-Aβ) cells. Bars indicate C99 and full-length APP. b Cell survival was assayed on day 3. Unpaired two-tailed t-test (n = 3/group), data are mean ± SD. c Diagram illustrating the experimental approach. At day 2, non-induced (-Aβ) and induced (+Aβ) MC65 nerve cells were harvested for transcriptomic, proteomic and metabolomic analysis. PCA of the (d) top 500 most expressed genes (n = 5/group), (e) top 500 most expressed proteins (n = 4/group) and (f) total metabolites (n = 5/group). Ellipses show the 95% confidence interval of a t-distribution. Fold change levels and respective adjusted P values for all parameters can be found in supplementary Tables S1, S2 and S3. g Number of DE genes, DE proteins and DE metabolites upregulated (up) and downregulated (down) with Aβ. Number of total genes, proteins and metabolites detected/measured is indicated as the denominator. DE cutoff for the three parameters was FDR < 0.05 and absolute logFC > 0.5. Distribution of the (h) DE genes and (i) DE proteins per major subcellular compartment according to the Human Protein Atlas¹⁴. Overlap ratio is the number of DE genes or DE proteins found altered per total genes or proteins described to be present in a given compartment. P values calculated by 1000 bootstrap are indicated.