Abstract:

Objective

To investigate the molecular pathological mechanisms of Alzheimer's disease（AD）through transcriptome analysis using Caenorhabditis elegans as a model organism，aiming to provide an in vivo experimental platform for oral-neural disease research.

Methods

Transcriptome sequencing was performed on wild-type N2 and AD model worms（CL2355）expressing pan-neuronal human Aβ_1-42 using Illumina HiSeq platform.Differential expression analysis，gene ontology（GO）enrichment analysis，Kyoto encyclopedia of genes and genomes（KEGG）pathway analysis，and gene set enrich analysis（GSEA）were conducted to systematically detect changes in gene expression.

Results

Compared to wild-type，1 899 upregulated and 2 018 downregulated genes were identified in the AD model. GO analysis revealed significant enrichment of upregulated genes in neurite guidance and cell differentiation，while downregulated genes were enriched in mRNA splicing and DNA repair. KEGG analysis showed significant upregulation of drug and xenobiotic metabolism pathways，and downregulation of RNA surveillance and endocytosis pathways.GSEA revealed significant downregulation of the apoptosis pathway［normalized enrichment score（NES）=-1.775，P = 0.008 1］with decreased expression of key genes including ced-9 and ced-3.

Conclusions

This study revealed systematic changes in gene expression in the C.elegans AD model，providing an ideal experimental model for investigating the role of oral infection factors in AD pathogenesis.

Key words: Alzheimer's disease, Caenorhabditis elegans, Transcriptome, Differential gene expression, Apoptosis pathway