A new ANMerge-based blood transcriptomic resource to support Alzheimer's disease research

INTRODUCTIONAlzheimers disease (AD) has greater prevalence in women and lacks effective treatments. Integrating multimodal data using machine learning (ML) may help improve diagnostics and prognostics. METHODSWe produced a large and updatable blood transcriptomic dataset (n=1021, with n=317 replicates). Technical robustness was assessed using sampling-at-random, batch adjustment and classification metrics. Transcriptomic and MRI features were concatenated to develop models for AD classification. RESULTSReprofiling of blood transcriptomics resolved previous technical artefacts (sampling-at-random AUC; Legacy=0.732 vs. New=0.567). AD-associated molecular pathways were influenced by cell counts and sex, including unchanged mitochondrial DNA-encoded RNA and altered B-cell receptor biology. Several genes linked to AD-associated neuroinflammatory pathways, including BLNK, TREM2, and MS4A1, showed significant enrichment. Concatenation of transcriptomics and MRI models modestly improved classification performance (AUC; MRI=0.922 vs. transcriptomics-MRI=0.930). DISCUSSIONWe provide a new large-scale and technically robust blood AD transcriptomic dataset, highlighting details of molecular sexual dimorphism in AD and potential literature false positives, while providing a novel resource for future multimodal ML and genomic studies.