Combined multi-omics and brain pathology reveal novel biomarkers for alzheimer's disease

Alzheimer's disease (AD) is a complex disorder with significant genetic contributions, yet only a limited number of risk loci have been conclusively identified. This research aimed to discover novel potential biomarkers for AD through multi-omics and brain pathology analysis. In this study, we investigated hippocampal molecular alterations in APP/PS1 mouse using transcriptomics and data-independent acquisition (DIA) proteomics. To further validate the involvement of differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) in AD pathology and potential drug treatment, we performed an integrative analysis incorporating pathological data and protein-protein interaction networks. We identified 263 DEGs and 448 DEPs. Integrative transcriptomic and proteomic analyses revealed five co-upregulated DEGs/DEPs and one co-downregulated DEG/DEP. Comparison of KEGG pathway enrichment between the two datasets showed significant involvement in the complement and coagulation cascade, as well as neurodegeneration-multiple diseases. Furthermore, mRNA levels of LY86, CD180, and C1QB were strongly associated with amyloid-β plaque load in the AD mouse hippocampus. Protein-protein interaction analysis suggested that APP, LY86, CD180, and C1QB could serve as potential therapeutic targets for AD. The study identified three novel AD loci (EGFL8, ERMN, and CD180), with CD180 showing association with AD at both the expression and pathological levels, highlighting their potential roles in disease progression and therapeutic intervention.