Comparative study of microRNA profiling in one Chinese Family with PSEN1 G378E mutation
MicroRNAs are not widely studied in familial Alzheimer’s disease cases, whether the microRNA profilings in familial Alzheimer’s disease patients are similar to the sporadic AD patients is not known. This study aims to investigate the differential expression of microRNAs (miRNAs) associated with early-onset familial Alzheimer’s disease (EO-FAD) in a Chinese family. We performed the gene mutation analysis in a family clinically diagnosed of EO-FAD. Micro-arrays were used to profile the miRNAs in cerebrospinal fluid of 2 affected members, 2 unaffected carriers and 2 mutation negative controls. The clinical presentation confirmed the EO-FAD diagnosis, and a recurrent mutation of the PSEN1 p.G378E was found in the family. The result showed that in the miRNAs expression profile, a total of 166 miRNAs were up-regulated and 3 miRNAs were down-regulated in the affected individuals compared with mutation negative individuals. But after Benjamini Hochberg FDR correction, only 25 miRNAs were significantly up-regulated and no miRNA was down-regulated, the levels of miR-30a-5p, miR-4758-3p and let-7a-3p were elevated significantly. Compared with mutation negative controls, 21 miRNAs were up-regulated and 18 microRNAs were down-regulated in the unaffected mutation carriers, after Benjamini Hochberg FDR correction, miR-345-5p was up-regulated and miR-4795-3p was down-regulated in the unaffected mutation carriers. And there was no difference between the affected members and unaffected mutation carriers. GO database showed that the top biological processes affected by the predicted target genes are nucleic acid binding transcription factor activity and transcription factor activity (sequence-specific DNA binding) (GO:0001071 and GO:0003700). The result of KEGG pathways showed 64 pathways were implicated in the regulatory network. The present study identified the miRNA profiling of Chinese siblings with G378E mutation in the PSEN1. Compared with mutation negative controls, the levels of 25 miRNAs including miR-30a-5p, miR-4758-3p and let-7a-3p were elevated significantly in the affected members, miR-345-5p was up-regulated and miR-4795-3p was down-regulated in the unaffected mutation carriers. Our study showed the microRNA profilings in the cases of a EO-FAD family with PSEN1 p.G378E mutation, but because of the individuals in the family was small, the results in other types of EO-FAD still need further studied.
KeywordsEO-FAD microRNA profiling miR-30-5p miR-4758-3p Let-7a-3p FOXO signaling pathway
early-onset familial Alzheimer’s disease
magnetic resonance imaging
amyloid precursor protein
Mini- Mental State Examination
instrumental activities of daily living scales
false discovery rate
toll-like receptor 7
Kyoto Encyclopedia of Genes and Genomes
Notch1 intercellular domain
We would like to thank the patients for their participation in this study.
Lv ZY and Hu LC contributed equally in RNA extraction and microRNA analysis. Zhang K, Sun ZZ, Zhang J, Zhang LP and Yang Y interviewed the patients and their family members, collected clinical data and CSF and blood samples. Hao YL was a major contributor in writing the manuscript. All authors read and approved the final manuscript.
This study was supported by the National Natural Science Foundation of China (grant No. 81401064, NO.81771360); PhD initial funding (2016-BS-011); Jining science and technology development project (Jikezi 56–6) and Natural Science Foundation of Shandong (ZR2017LH031).
Compliance with ethical standards
The authors declare that they have no competing interests.
Consent for publication
Written informed consent for publication was obtained from patients. A copy of the written consent is available for review to the Editor of this journal.
Ethics approval and consent to participate
The study protocol was approved by the Ethics Committees of the Affiliated Hospital of Jining Medical University, and all participants provided written informed consent.
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