Genome-wide profiling and predicted significance of post-mortem brain microRNA in Alzheimer’s disease

• Published in: Mechanisms of ageing and development Vol. 191; p. 111352
• Main Authors: Henriques, Adriane D., Machado-Silva, Wilcelly, Leite, Renata E.P., Suemoto, Claudia K., Leite, Kátia R.M., Srougi, Miguel, Pereira, Alexandre C., Jacob-Filho, Wilson, Nóbrega, Otávio T.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.10.2020
• Subjects: Alzheimer’s disease; Array analysis; DIANA miRPath; microRNA; DIANA miRPath; microRNA; Array analysis; Alzheimer’s disease
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/j.mad.2020.111352

•miRNAs were profiled in post-mortem brains of people with the NIA-AA A+T+ phenotype.•A high-throughput microarray expression platform and validation assays were used.•Six miRNAs were differentially expressed compared to age- and sex-matched donors.•Bioinformatics implicated 3 miRNAs, 7 target genes and 11 pathways with AD pathology.•Such dysregulation suggests apoptosis, autophagy and oxidation in the CNS. MicroRNAs (miRNAs) emerged as regulatory elements, with up to 70 % of all miRNAs found in the brain, playing key roles in the onset of Alzheimer’s disease (AD). to broadly assess the expression levels of miRNAs in post-mortem brain (PMB) samples of individuals deceased with or without AD. A high-throughput microarray platform was used to sketch miRNA samples isolated from superior and middle temporal gyrus of A+T+ AD cases, compared to samples from age- and sex-matched AD-devoid donors, all pulled from the University of São Paulo’s Brain Biobank. The miRNAs identified by microarray were subjected to validation with specific qRT-PCR assays employing independent PMB samples. The analyses yielded 6 miRNAs differentially expressed (miR-30e_3p; miR-365b_5p; miR-664_3p; miR-1202; miR-4286; miR-4449), and their interplay with specific AD-related genes and signaling pathways was explored using bioinformatics analyses (including the KEGG package, mirPath v.3). In the end, 3 miRNAs, 7 target genes and 11 pathways were found closely interrelated and implicated with the AD pathophysiology. A dysregulation on a subset of these miRNAs appear to affect a range of genes (notably PTEN) and pathways (emphasis to PI3K-AKT) so to provide grounds for neuronal death by apoptotic signaling, autophagy and/or oxidative damage.