Circulating MicroRNAs As Biomarkers Of Alzheimer’s Disease System Review And A Meta-analysis

Background:Approximately 35.6 million people in the world have dementia,60 % of whom are patients with Alzheimer’s disease(AD).In 2030,the number is expected to rise to 65.7 million,and in 2050,the number will reach 115.4 million.Every year,it is estimated to cost up to $172 billion for treatment and nursing care for AD in America,which is an enormous burden for society.Although AD is one of the fastest-growing major disease burdens,there are still no available treatments to alter the natural history of this disease.The pathological changes in the AD brain can appear at least 20 years before the clinical symptoms.Because the late stages of neurodegenerative diseases have massive neuronal death,the treatment of these diseases is extremely difficult.The barriers to effective therapy include the lack of a specific biomarker for the early identification of these diseases before the onset of clinically apparent cognitive impairment.Objective:MicroRNA(miRNA),a category of about 22 nucleotides noncoding RNA,can regulate the expression of genes posttranscriptionally via base-pairing with their targets messenger RNA(mRNA),have been recognized as novel biomarkers of diseases.In this systematic review,we identify miRNAs that are differentially expressed in Alzheimer’s disease(AD)and evaluate their accuracy as potential blood biomarkers.Methods:The Chinese search terms were ‘microRNA’ in combination with(AND)‘Alzheimer’s disease’.The databases WanFang,CNKI,VIP were searched.At the same time,the English search terms were ‘microRNA’ in combination with(AND)‘Alzheimer’s disease’,OR ‘cognitive impairment’,OR ‘dementia’.The databases MEDLINE,PUBMED,Cochrane and EMBASE were searched.The data regarding the specificity and sensitivity of miRNAs to predict AD were extracted from the original studies.The revised quality assessment of studies of diagnostic accuracy(QUADAS-2)was used to assess the quality of each included study.STATA 14.0 and Meta-analyst software were used to pool the initial data.The evaluation index,including the overall sensitivity,specificity,positive likelihood ratios(PLR),negative likelihood ratios(NLR),diagnostic odds ratios(DOR),and area under the summary receiver operator characteristic(SROC)curve(AUC),was used to evaluate the diagnostic performance of circulating miRNAs for AD.To explore the sources of heterogeneity,subgroup analyses and meta-regression analyses were performed.Results:In the end,twelve eligible studies were included.The overall sensitivity was 0.80(95% CI 0.76-0.83),specificity was 0.84(95% CI 0.80-0.88),PLR was 3.35(95% CI 2.96-3.79),NLR was 0.26(95% CI 0.22-0.30),and DOR was 15(95% CI 11-19).Subgroup analysis suggested that the Caucasian group and Plasma group showed a better performance in AD diagnosis and that the DOR was 32(95% CI 20-52)and 42(95% CI 25-70),respectively.Conclusion:This meta-analysis showed that miRNAs may be promising biomarkers in the human circulatory system for the clinical diagnosis of AD.We also verified that Caucasian group and Plasma group may yield more diagnostic accuracy.