The fusiform gyrus exhibits differential gene-gene co-expression in Alzheimer's disease

Abstract

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.

Identification of deregulated lncRNAs in Alzheimer’s disease: an integrated gene co-expression network analysis of hippocampus and fusiform gyrus RNA-seq datasets

“…Several co-expression and differential co-expression network analyses have already been applied on RNA-seq data from hippocampus and fusiform gyrus, leading to the identification of co-expressed networks and genes associated with AD ( Sato et al, 2019 ; Crist et al, 2021 ; Xia et al, 2022 ; Ribeiro-dos-Santos et al, 2023 ). As our aim was the identification of lncRNAs that could take part of the pathologic molecular mechanisms of AD, we prioritized modules comprising the majority of lncRNAs which could be identified as driver genes and could be postulated to influence the expression of other genes or that could be directly involved in the causal mechanisms of AD.…”

Dissecting the Puzzling Roles of FAM46C: A Multifaceted Pan-Cancer Tumour Suppressor with Increasing Clinical Relevance

“…The last model we will discuss was suggested by our lab [21] and proposes that, by localizing at the ER thanks to interaction with fibronectin type III domain containing 3A and 3B (FNDC3A and FNDC3B) [21,66], two proteins known to be involved in cell development [76,77], but also with disease [78,79], and specifically cancer [80][81][82][83][84][85], FAM46C regulates intracellular trafficking (Figure 1C). In our work, we found that expression of FAM46C in MM cell lines was coupled with only a really mild alteration of RNA levels and a really weak poly(A) activity, comparable to that of the loss-of-function FAM46C variant D90G.…”