Analysis of gene expression profiles associated with neuroinflamm | 49868

Journal of Neurology & Neurophysiology

ISSN - 2155-9562

Analysis of gene expression profiles associated with neuroinflammatory pathways in Colombian patients with Alzheimers disease

26th European Neurology Congress

August 06-08, 2018 | Madrid, Spain

Kelly Yojanna Cardona Londo, Mauricio Medina-Salcedo, Mary Orrego-Cardozo, Francia Restrepo-de Mejia and Carlos Andres Naranjo-Galvis

Universidad Autónoma de Manizales, Colombia

Posters & Accepted Abstracts: J Neurol Neurophysiol

Abstract :

Introduction: Alzheimerâ??s disease (AD) is the most common neurodegenerative disorder worldwide, mainly affecting the population over 65 years of age. AD is characterized by progressive deterioration of short-term memory, eventually involving other aspects of cognition, including language impairment, executive dysfunction, and visuospatial impairment, leading to the loss of independent daily living capacities. The pathophysiological mechanism of AD remains unclear; however, recent studies demonstrated that inflammation may be involved in neurodegenerative dementia. Cellular immune components, such as microglia or astrocytes, mediate the release of inflammatory molecules, including tumor necrosis factor-?± (TNF-?±), growth factors, adhesion molecules, or chemokines. Over and under expression of pro and anti-inflammatory molecules, respectively, may result in neuroinflammation and, thus, disease initiation and progression. This study aimed to explore the molecular pathogenesis of AD-related inflammation through the analysis of differentially expressed genes in AD patients and controls. Methods: Whole blood samples from five AD patients and ten non-demented controls were sequenced using the Ion AmpliSeq Transcriptome Human Gene Expression panel from Ion Torrent. Differentially expressed genes (DEGs) were identified by the DeSeq2 package in R/Bioconductor. In addition, functional enrichment analysis through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were carried out in order to identify candidate AD-related genes. Finally, proteinâ??protein interaction (PPI) networks were analyzed, using the STRING database. Results: A total of 95 up-regulated and 149 down-regulated genes were identified. The up-regulated genes were enriched for the following GO-Biological Processes: interferon-gamma mediated signaling pathway, cellular response to interferon-?³ (IFN-?³), and type I interferon-signaling pathway; while the down-regulated genes were mainly associated with cell cycle and mitosis. In relation to KEGG metabolic pathways mapping, we highlight gene expression alterations in the signaling pathways of JAK/STAT, chemokines, tumor necrosis factor-?± (TNF-?±), interleukin-17 (IL-17), MAP kinases and Alzheimer's disease. Conclusion: Our study provides a comprehensive picture of gene expression landscape in AD, identifying key processes associated with AD pathology. Candidate AD-related DEGs, including JAK2, STAT1, STAT2, PLC and MAP3K7, may be important for the regulation of neuroinflammation contributing to the progress and development of AD.

Biography :