title: Can Peripheral MicroRNA Expression Data Serve as Epigenomic (Upstream) Biomarkers of Alzheimer's Disease?
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. However, biomarkers that require testing in the brain tissue pose a formidable practical barrier to AD diagnostic innovation. MicroRNAs (miRNAs) are responsible for control of gene expression at the posttranscriptional level and are essential for the function of neuronal networks and neuronal survival. miRNA expression can impact the regulation of APP (amyloid beta A4 precursor protein), PSEN1 (presenilin 1), PSEN2 (presenilin 2), and BACE1 (beta-secretase 1) genes in the brain that were previously implicated in AD pathophysiology. Little is known, however, on the extent to which peripheral tissue (e.g., whole blood) miRNA variation might offer clinical predictive value for AD. Moreover, few studies have examined multiple peripheral miRNA expression data at the same time. We report here, to the best of our knowledge, the first whole-blood-based and parallel study of seven miRNAs (hsa-miR-9-5p, hsa-miR-29a-3p, hsa-miR-106a-5p, hsa-miR-106b-5p, hsa-miR-107, hsa-miR-125a-3p, and hsa-miR-125b-5p) in relation to AD susceptibility. Notably, these miRNAs are situated "upstream" to the genes implicated in AD. We measured the whole-blood miRNA expression by a real-time polymerase chain reaction in a large study sample (n = 281), comprising patients with AD (n = 172) and healthy controls (n = 109). A reduction in whole-blood expression of hsa-miR-9-5p, hsa-miR-106a-5p, hsa-miR-106b-5p, and hsa-miR-107 was significantly associated with an increased risk of AD (p < 0.05). Notably, after receiver operating characteristics curve analyses, hsa-miR-106a-5p displayed, as a predictor variable, 93% specificity and 68% sensitivity. On the other hand, the expression of hsa-miR-29a-3p, hsa-miR-125a-3p, and hsa-miR-125b-5p was not significantly different between patients and controls (p > 0.05). In conclusion, these observations warrant replication in larger samples while making a contribution to translational research, precision medicine, and biomarker literatures, by expanding the current efforts for AD diagnostic innovation to the realm of epigenomic pathways such as miRNA expression variation among patients.
authors: 1 Department of Nutrition and Dietetics, Faculty of Health Sciences, Gaziantep University , Gaziantep, Turkey .
authors: Şenay Görücü
authors: ŞG
authors: Yılmaz
authors: 2 Department of Medical Biology, Faculty of Medicine, Mersin University , Mersin, Turkey .
authors: Mehmet Emin
authors: ME
authors: Erdal
authors: 3 Department of Neurology, Faculty of Medicine, Mersin University , Mersin, Turkey .
authors: Aynur Avcı
authors: AA
authors: Özge
authors: 4 Department of Biostatistics and Medical Informatics, Faculty of Medicine, Düzce University , Düzce, Turkey .
authors: Mehmet Ali
authors: MA
authors: Sungur
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D057890:Epigenomics; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; C542541:MIRN106 microRNA, human; C549045:MIRN107 microRNA, human; C531888:MIRN125 microRNA, human; C532045:MIRN29a microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs