COMPREHENSIVE MULTI-OMICS STUDY TO EXPLORE THE DYSFUNCTIONAL MECHANISM OF ALZHEIMER'S DISEASE

Sha Liu^1#, Xin Cui^2#, Wenjing Shi³, Ming Wu⁴, Qiaona Wu⁴, Kun Di⁴, Liying Wu^5*, Huanbin Zhao^6*

¹Department of Pharmacy, the Third Hospital of Shijiazhuang, School of Physical Education, Hebei Normal University, Shijiazhuang, 050011, China - ²Yanjing Medical College of Capital Medical University, Beijing, 101300, China - ³Pharmacy department of Hebei General Hospital, Pharmacology Department of Hebei Medical University, Hebei, 050000, China - ⁴Department of Pharmacy,the Third Hospital of Shijiazhuang, Shijiazhuang , 050011,China - ⁵Department of Pharmacy, Bethune Internatinal Peace Hospital of Chinese PLA, 050082, China - ⁶School of Physical Education, Hebei Normal University, Shijiazhuang, 050024, China

0024, China

Background: With the aging of society, Alzheimer's disease (AD) has become a severe problem. Its pathogenesis is complex and overlaps with healthy aging, and it cannot be conclusively diagnosed and treated. 

Materials and methods: This study comprehensively analyzed its dysfunctional mechanisms through multi-omics. In the GEO database, we collected microarray data from 9 hippocampal gene samples from the control group and 22 hippocampal gene samples from the diseased group and collected whole-genome DNA methylation data.

Result: The dysfunctional mechanisms were explored by differential genetic analysis, co-expression analysis, enrichment analysis, regulator prediction, and methylation analysis. Three sets of differential gene analysis yielded 164, 1715 and 2689 differential genes, respectively. Three thousand seven hundred eighty-six differential genes were obtained by combining the three groups of differential genes and de-duplicating them (P<0.05). Five functional barrier modules were obtained by weighted gene co-expression network analysis. The critical genes for each module are SUB1, CYP2C9, MZT2B, SV2A, and CYP11B2. 

Conclusion: The results of the enrichment analysis show that the dysfunctional module is mainly related to cell-cell signaling by wnt and Wnt signaling pathway. Through the pivotal analysis of TF and ncRNA, we predicted the regulators of the dysfunctional module and obtained key regulators (SP1, SHOX2, miR-519-5p, miR-520e, miR-320d). Methylation analysis revealed that there were 162 methylated modified genes, but the degree of methylation was relatively low. Based on the analysis of multi-omics, we believe that the dysfunctional mechanism of AD is due to the regulation of Wnt channels by genes (SP1, SHOX2), which leads to pathological changes.