[P3–213]: MIRNAS AND THEIR ROLE IN THE CORRELATION BETWEEN MAJOR DEPRESSIVE DISORDER, MILD COGNITIVE IMPAIRMENT AND ALZHEIMER's DISEASE

Previous studies have demonstrated the relevance of cerebrovascular changes, abnormalities in amyloid-β protein metabolism and changes in inflammatory, neurotrophic and endocrine-metabolic markers in depression in the elderly. Similar patterns of abnormalities in these neurobiological cascades were also found in patients with Alzheimer's Disease (AD) and in patients with amnestic Mild Cognitive Impairment (MCI) who progressed to AD during longitudinal follow-up. These results suggest that depression and neurocognitive disorders share neurobiological modulations that promote progressive changes in the central nervous system and ultimately determine a higher risk of dementia on elderly people with major depressive disorder (MDD). This study aims to identify plasma biomarkers associated with cognitive impairment in the elderly with depression. Plasma samples were collected from 13 MDD, 11 MDD with MCI patients and 19 healthy controls. Plasma miRNA profiling was performed by Ion Proton sequencing using RNA extracted from plasma samples. The bioinfo and statistical analysis used the R DESEq and DESEq2 packages and the scripts from Pearl. The preliminary analysis of the genes and the biological pathways that were possibly regulated these microRNAs were did using the Gene Ontology database, Kyoto encyclopedia of genes and genomes and DIANA. From the sequencing of 43 patients we identified 10 microRNAs differently expressed (miR-100–5p, miR-184, miR-1–3p, miR-125b-5p, miR-5572, let-7a-5p, miR-140–3p, miR-454–3p, miR-373–3p, miR-218–5p) between control and MDD groups (Table 1). Among those 10, miR-184 and miR-1–3p were differently expressed between MDD and MDD with MCI (Table 2). Using DIANA database we identified 415 genes (Table 3) with miTG score higher than or equal to 0,99, which were predicted as targets of these microRNAs. Some of the signaling pathways found were proteostasis control, maintenance of genomic integrity, regulation of transcriptional activity, immune-inflammatory control, and neurotrophic support. The development of this research may allow an early recognition of individuals with depression and cognitive impairment, who have an increased risk of developing dementia, and the selection of more specific biomarkers for the treatment and prevention of cognitive decline and dementia in the elderly with depression.