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P3‐175: Biological Pathways Found in Common Between Alzheimer’s Disease and Major Depression: A Study on Microrna Expression in a Systematic Review

2016; Wiley; Volume: 12; Issue: 7S_Part_18 Linguagem: Inglês

10.1016/j.jalz.2016.06.1835

1552-5279

Ana Paula Mendes M Silva, Eduardo de Souza S. Nicolau, Kelly Silva Pereira, Kenia Kelly Fiaux do Nascimento, Camila Moreira Silva MS Ferreira, Gesiane Thamire Tolentino TT Araujo, Breno S. Diniz, Antônio Lúcio Teixeira,

MicroRNA in disease regulation

Major Depressive Disorder (MDD) and Alzheimer's disease (AD) present a clinical-epidemiological relationship suggesting that neurobiological abnormalities may be found in common in both conditions. Presenting complexity and probably bidirectional relationship, despite well-defined differences in clinical manifestations. In young and older adults, even after successful antidepressant treatment, Cognitive Impairment due to depressive episodes is common and persistent. Furthermore, higher rates of depressive symptoms are prior to AD patients than those in older adults or elderly people in the general population. A systematic literature review was conducted using PubMed, Web of science and Scopus databases. MeSH terms "(microRNA OR miRNA) and Alzheimer's disease" were used in the AD research and the terms "(microRNA OR miRNA) and (Major depressive disorder OR Depressive disorder OR depression)" were used to do the MDD research. After identifying eligible articles, we verified the authenticity of mature microRNAs using Mirbase. In order to determine the interaction between the miRNA and the gene we used DIANA database, considering only genes with miTG score higher or equal to 0,99. Finally, we used Cytoscape to create a shared network between MDD and AD. Through the systematic review, we identified 74 differently expressed microRNAs for AD and 31 for MDD with p-value below 5% and log2foldchange greater than |1.5|. Eight (8) microRNAs (Table 1) were abnormally regulated in both disorders (hsa-let-7f-5p / hsa-miR-30d-3p / hsa-miR-664a-3p / hsa-miR-361-5p / hsa-let-7g-5p / hsa-let-7d-5p / hsa-miR-191-5p / hsa-miR-30d-5p), with p-value below 5% and log2foldchange greater than |1.5|. Using DIANA we identified 167 genes with miTG score higher or equal to 0.99. Main biological pathways and processes regulated by these genes were proteostasis control, maintenance of genomic stability, regulation of transcriptional activity, immune-inflammatory control, and neurotrophic support (Table 2 and Figure 1). The overview chart presents name of functional groups for genes based leading term, which is the most significant term in the group The current results suggest that maintenance of genomic integrity, proteostasis control, immune-inflammatory regulation, and neurotrophic support are key neurobiological links between these conditions. Our results provide a comprehensive model to understand how MDD increases the risk of development of AD.