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

Made available in DSpace on 2021-06-25T11:23:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-10-01 Fundacao de Amparo a Pesquisa do Distrito Federal (FAP-DF) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Background: 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). Objective: to broadly assess the expression levels of miRNAs in post-mortem brain (PMB) samples of individuals deceased with or without AD. Methods: A high-throughput micmarray 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 Sao Paulo's Brain Biobank. The miRNAs identified by microarray were subjected to validation with specific qRT-PCR assays employing independent PMB samples. Results: The analyses yielded 6 miRNAs differentially expressed (miR-30e_3p; miR-365b_5p; miR-664_3p; miR1202; 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. Conclusion: 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. Fed Univ Brasilia UnB, Brasilia, DF, Brazil State Univ Sao Paulo USP, Sao Paulo, SP, Brazil McGill Univ Hlth Ctr MUHC, Montreal, PQ, Canada State Univ Sao Paulo USP, Sao Paulo, SP, Brazil Fundacao de Amparo a Pesquisa do Distrito Federal (FAP-DF): 193.000.967/2015 CNPq: 445692/2014-6 CAPES: 001 CNPq: 303,540/2019 2