Fig. 4: Mouse models with additional pathologies beyond amyloidosis increase the similarity to AD.

a Proteomic profiling of two more mouse models that express additional AD pathologies: WT (n = 8) and 3xTG (Aβ and tau pathologies, n = 19), as well as WT (n = 4) and BiG (Aβ and U1 splicing pathologies, n = 4). All mice were ~6 months old. The proteomic data were subjected to DE analysis and comparison with human AD data. b, c Volcano plots of log₂FC and FDR in 3xTG and BiG mice, compared to WT, with DEPs highlighted in colors and cutoffs indicated by dashed lines. d, e Selected protein-protein interactions of significantly altered DEPs found exclusively in individual mice, such as MAPT interactome in 3xTG, and splicing/synaptic interactome in BiG. f Numbers of DEPs in AD mouse models that were consistently altered in AD. The percentage was calculated using a denominator of 654 AD DEPs that were detectable by MS in mice. g Strategy for ranking individual proteins by multi-omics using order statistics. (i) All age-dependent proteomic data from 5xFAD and NLGF were initially consolidated into two datasets for the amyloidosis proteome and phosphoproteome. (ii) These datasets were then integrated with 10 additional datasets, which include the mouse transcriptome (5xFAD), 3xTG/BiG proteomes, human genetic data from GWAS, human transcriptomes, proteomes (MCI and two independent AD studies, n = 3), phosphoproteome, and interactome datasets. h Protein integrative rankings defined by combining 12 datasets. The entire datasets were ranked based on all identified genes/proteins. Subsequently, we extracted the rankings for the AD-mouse shared proteins (n = 275). The top 20 proteins are displayed, with missing values represented by white boxes.