Objective To conduct an in-depth analysis on the correlation of miRNA and Alzheimer disease (AD) pathogenesis and provide an experimental basis for AD potential biomarkers by analysis of serum miRNA expression profiles in AD patients. Methods The miRNA expression profiles were exmined in 7 severe AD patients and 5 normal controls using high-throughput sequencing and bioinformatic analysis. Results Compared with the normal controls, there were serum differential expression of 112 miRNAs (DEmiRNAs) including 57 being up-regulated and 55 being down-regulated in patients with severe AD (P<0.05). GO-term function enrichment analysis showed that DEmiRNAs participated in the protein binding, ion binding, transcription metal binding, and biological metabolism and regulation process of organelle and cell membrane, etc. KEGG pathway enrichment analysis found that PI3K-Akt signal pathway was an important pathway of target genes. Conclusion The differential expression of serum miRNAs may be potential biomarkers of AD and the target genes of DEmiRNAs are related to the pathological changes of AD.