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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
21 Downloads (Pure)


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.

Original languageEnglish
Article number987
Pages (from-to)1-14
Number of pages14
Issue number6
Publication statusPublished - 1 Mar 2022

Bibliographical note

Copyright the Author(s) 2022. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


  • Alzheimer’s disease
  • Differentially expressed genes
  • GABAergic synapse pathway
  • Retrograde endocannabinoid signaling


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