Fig. 6

Associations between individual proteins across brain samples and estimated effect size in assays of neuronal structure and function. A, B Waterfall plots showing top associated proteins in the neurite integrity (A) and spontaneous activity (B) assays, calculated with the Spearman correlation coefficient. C Table of proteins meeting a p-value of < 0.05 across both assays. Top associations in both assays included ABI1, which showed a protective association in the assay, and GM2A which showed a neurotoxic association. D GSEA analyses using the REACTOME database for associations with the MEA and NI assays identify Diseases of metabolism and Effectors of Rho GTPase signaling/WASP and WAVE complexes with effect size in both assays. E Schematic of WAVE regulatory complex (WRC) and ARP complexes, gene symbols in red were identified as leading-edge genes in the GSEA analysis in (D). F Scatter plot of ABI1/ABI2 across TBS-brain extracts by category. Error bars represent mean. Statistical analyses used one-way-ANOVA with Dunn’s multiple comparisons test. *, p < 0.05. G Schematic of GM2A removing GM2 from the membrane for hydrolysis mediated by HEXA/HEXB. All 3 proteins were in the leading edge of the Diseases of metabolism term. H Scatter plot of GM2A across TBS-brain extracts by category reveal higher levels in AD. Error bars represent mean  ± SEM. Statistical analyses used one-way-ANOVA with Dunn’s multiple comparisons test. *, p < 0.05. I GM2A levels are elevated in CSF of AD compared to controls (data from [39]). Statistical analyses used unpaired t-test with Welch correction. *, p < 0.05