Unveiling the Genetic Network of Alzheimer’s in the Fusiform Gyrus

Published on May 15, 2023

The mysterious world of Alzheimer’s Disease (AD) is like a puzzle, with many missing pieces. One key piece appears to be the fusiform gyrus, a region in the brain that plays an important role in memory and cognition. In this study, scientists investigated the genes and gene interactions in the fusiform gyrus of individuals with AD and those without. They discovered four genes, FNDC3A, MED23, NRIP1, and PKN2, which formed exclusive hubs in gene co-expression networks related to AD. Additionally, they found three genes, FAM153B, CYP2C8, and CKMT1B, that displayed differential co-expression links between AD and healthy individuals. These findings provide valuable insights into the molecular mechanisms underlying AD development and highlight the significance of gene regulatory networks in the fusiform gyrus. Further analysis revealed enrichments in Toll-Like Receptors Cascades and signaling pathways involved in G protein events, PIP2 hydrolysis, and EPH-Epherin mechanism within the fusiform gyrus. The study opens up new avenues for research into potential therapeutic targets for AD and invites curious minds to explore the fascinating world of genetics in Alzheimer’s disease!

Alzheimer’s Disease (AD) is an irreversible neurodegenerative disease clinically characterized by the presence of β-amyloid plaques and tau deposits in various regions of the brain. However, the underlying factors that contribute to the development of AD remain unclear. Recently, the fusiform gyrus has been identified as a critical brain region associated with mild cognitive impairment, which may increase the risk of AD development. In our study, we performed gene co-expression and differential co-expression network analyses, as well as gene-expression-based prediction, using RNA-seq transcriptome data from post-mortem fusiform gyrus tissue samples collected from both cognitively healthy individuals and those with AD. We accessed differential co-expression networks in large cohorts such as ROSMAP, MSBB, and Mayo, and conducted over-representation analyses of gene pathways and gene ontology. Our results comprise four exclusive gene hubs in co-expression modules of Alzheimer’s Disease, including FNDC3A, MED23, NRIP1, and PKN2. Further, we identified three genes with differential co-expressed links, namely FAM153B, CYP2C8, and CKMT1B. The differential co-expressed network showed moderate predictive performance for AD, with an area under the curve ranging from 0.71 to 0.76 (+/− 0.07). The over-representation analysis identified enrichment for Toll-Like Receptors Cascades and signaling pathways, such as G protein events, PIP2 hydrolysis and EPH-Epherin mechanism, in the fusiform gyrus. In conclusion, our findings shed new light on the molecular pathophysiology of AD by identifying new genes and biological pathways involved, emphasizing the crucial role of gene regulatory networks in the fusiform gyrus.

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