Blood-based microRNAs as the potential biomarkers for Alzheimer's disease: evidence from a systematic review

Alzheimer's disease (AD) is a neurodegenerative disorder that progresses over time and is identified by the development of neurofibrillary tangles and amyloid deposits in the brain. Mounting evidence has revealed that microRNAs (miRNAs) are significantly involved in AD progression, and may be used as promising biomarkers for diagnosis and prognosis. Nevertheless, the existing body of data regarding dysregulated circulating miRNAs in AD and their therapeutic applications are characterized by a lack of consistency. A comprehensive search was performed across various databases (PubMed, EMBASE, Web of Science, Scopus, Google Scholar, Cochrane, and ProQuest), starting from its inception and ending in January 2023. The criteria for inclusion consisted of original research studies written in English, which utilized Real-Time PCR to analyze miRNA expression in the blood, serum, or plasma of AD patients and healthy controls. The extracted data included the miRNA(s) investigated, dysregulation status, study type, human sample(s), and major findings. The search produced 608 records, which after careful examination, resulted in 48 suitable articles for data extraction. The research revealed a wide range of sample types used, with whole blood (39.59%) and serum (27.09%, including serum-exosome at 4.17%) emerging as the most prominent. The compiled dataset featured 4001 AD patients and 3886 healthy controls, revealing intricate regulatory patterns among 83 up-regulated (35.78%), 66 down-regulated (28.44%), and 83 not significantly altered (35.78%) miRNAs. Our results demonstrated that specific circulating miRNAs are consistently dysregulated in AD and could serve as non-intrusive biomarkers for the identification, prognosis, and prediction of cognitive decline. Further large-scale prospective studies are required to validate their clinical applications.