Key Genes and Biochemical Networks in Various Brain Regions Affected in Alzheimer’s Disease
Morteza Abyadeh,
Nahid Tofigh,
Saeedeh Hosseinian,
Mafruha Hasan,
Ardeshir Amirkhani,
Matthew J. Fitzhenry,
Veer Gupta,
Nitin Chitranshi,
Ghasem H. Salekdeh,
Paul A. Haynes,
Vivek Gupta,
Koorosh Shahpasand,
Mehdi Mirzaei
Affiliations
Morteza Abyadeh
Faculty of Basic Sciences and Advanced Medical Technologies, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran
Nahid Tofigh
Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran
Saeedeh Hosseinian
School of Biological and Behavioural Sciences, Queen Mary University of London, London E1 4NS, UK
Mafruha Hasan
School of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia
Ardeshir Amirkhani
Australian Proteome Analysis Facility, Macquarie University, Sydney, NSW 2109, Australia
Matthew J. Fitzhenry
Australian Proteome Analysis Facility, Macquarie University, Sydney, NSW 2109, Australia
Veer Gupta
School of Medicine, Deakin University, Geelong, VIC 2600, Australia
Nitin Chitranshi
Department of Clinical Medicine, Faculty of Medicine, Health and Human Sciences, Macquarie Medical School, Macquarie University, Macquarie Park, North Ryde, Sydney, NSW 2109, Australia
Ghasem H. Salekdeh
School of Natural Sciences, Macquarie University, Macquarie Park, NSW 2109, Australia
Paul A. Haynes
School of Natural Sciences, Macquarie University, Macquarie Park, NSW 2109, Australia
Vivek Gupta
Department of Clinical Medicine, Faculty of Medicine, Health and Human Sciences, Macquarie Medical School, Macquarie University, Macquarie Park, North Ryde, Sydney, NSW 2109, Australia
Koorosh Shahpasand
Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran
Mehdi Mirzaei
Department of Clinical Medicine, Faculty of Medicine, Health and Human Sciences, Macquarie Medical School, Macquarie University, Macquarie Park, North Ryde, Sydney, NSW 2109, Australia
Alzheimer’s disease (AD) is one of the most complicated progressive neurodegenerative brain disorders, affecting millions of people around the world. Ageing remains one of the strongest risk factors associated with the disease and the increasing trend of the ageing population globally has significantly increased the pressure on healthcare systems worldwide. The pathogenesis of AD is being extensively investigated, yet several unknown key components remain. Therefore, we aimed to extract new knowledge from existing data. Ten gene expression datasets from different brain regions including the hippocampus, cerebellum, entorhinal, frontal and temporal cortices of 820 AD cases and 626 healthy controls were analyzed using the robust rank aggregation (RRA) method. Our results returned 1713 robust differentially expressed genes (DEGs) between five brain regions of AD cases and healthy controls. Subsequent analysis revealed pathways that were altered in each brain region, of which the GABAergic synapse pathway and the retrograde endocannabinoid signaling pathway were shared between all AD affected brain regions except the cerebellum, which is relatively less sensitive to the effects of AD. Furthermore, we obtained common robust DEGs between these two pathways and predicted three miRNAs as potential candidates targeting these genes; hsa-mir-17-5p, hsa-mir-106a-5p and hsa-mir-373-3p. Three transcription factors (TFs) were also identified as the potential upstream regulators of the robust DEGs; ELK-1, GATA1 and GATA2. Our results provide the foundation for further research investigating the role of these pathways in AD pathogenesis, and potential application of these miRNAs and TFs as therapeutic and diagnostic targets.
