Integrated transcriptomics reveals the brain and blood biomarkers in Alzheimer's disease

Abstract Background The systematic molecular associations between the peripheral blood cells and brain in Alzheimer's disease (AD) remains unclear, which hinders our understanding of AD pathological mechanisms and the exploration of new diagnostic biomarkers. Methods Here, we performed an integrated analysis of the brain and peripheral blood cells transcriptomics to establish peripheral biomarkers of AD. By employing multiple statistical analyses plus machine learning, we identified and validated multiple regulated central and peripheral network in patients with AD. Results By bioinformatics analysis, a total of 243 genes were differentially expressed in the central and peripheral systems, mainly enriched in three modules: immune response, glucose metabolism and lysosome. In addition, lysosome related gene ATP6V1E1 and immune response related genes (IL2RG, OSM, EVI2B TNFRSF1A, CXCR4, STAT5A) were significantly correlated with Aβ or Tau pathology. Finally, receiver operating characteristic (ROC) analysis revealed that ATP6V1E1 showed high‐diagnostic potential for AD. Conclusion Taken together, our data identified the main pathological pathways in AD progression, particularly the systemic dysregulation of the immune response, and provided peripheral biomarkers for AD diagnosis.