Temporal Cortex Microarray Analysis Revealed Impaired Ribosomal Biogenesis and Hyperactivity of the Glutamatergic System: An Early Signature of Asymptomatic Alzheimer's Disease

Ankita Kumari; Abdul Rahaman; Xin-An Zeng; Muhammad Adil Farooq; Yanyan Huang; Runyu Yao; Murtaza Ali; Romana Ishrat; Rafat Ali

doi:10.3389/fnins.2022.966877

Temporal Cortex Microarray Analysis Revealed Impaired Ribosomal Biogenesis and Hyperactivity of the Glutamatergic System: An Early Signature of Asymptomatic Alzheimer's Disease

Front Neurosci. 2022 Jul 25:16:966877. doi: 10.3389/fnins.2022.966877. eCollection 2022.

Authors

Ankita Kumari^{1

2

3}, Abdul Rahaman^{1

2

3}, Xin-An Zeng^{1

2

3}, Muhammad Adil Farooq⁴, Yanyan Huang², Runyu Yao^{1

3}, Murtaza Ali^{1

2

3}, Romana Ishrat⁵, Rafat Ali⁵

Affiliations

¹ School of Food Science and Engineering, South China University of Technology, Guangzhou, China.
² Guangdong Key Laboratory of Food Intelligent Manufacturing, Foshan University, Foshan, China.
³ Overseas Expertise Introduction Centre for Discipline Innovation of Food Nutrition and Human Health (111 Centre), Guangzhou, China.
⁴ Institute of Food Science and Technology, Khwaja Fareed University of Engineering and Information Technology, Rahim Yar Khan, Pakistan.
⁵ Center for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.

Abstract

Pathogenic aging is regarded as asymptomatic AD when there is no cognitive deficit except for neuropathology consistent with Alzheimer's disease. These individuals are highly susceptible to developing AD. Braak and Braak's theory specific to tau pathology illustrates that the brain's temporal cortex region is an initiation site for early AD progression. So, the hub gene analysis of this region may reveal early altered biological cascades that may be helpful to alleviate AD in an early stage. Meanwhile, cognitive processing also drags its attention because cognitive impairment is the ultimate result of AD. Therefore, this study aimed to explore changes in gene expression of aged control, asymptomatic AD (AsymAD), and symptomatic AD (symAD) in the temporal cortex region. We used microarray data sets to identify differentially expressed genes (DEGs) with the help of the R programming interface. Further, we constructed the protein-protein interaction (PPI) network by performing the STRING plugin in Cytoscape and determined the hub genes via the CytoHubba plugin. Furthermore, we conducted Gene Ontology (GO) enrichment analysis via Bioconductor's cluster profile package. Resultant, the AsymAD transcriptome revealed the early-stage changes of glutamatergic hyperexcitability. Whereas the connectivity of major hub genes in this network indicates a shift from initially reduced rRNA biosynthesis in the AsymAD group to impaired protein synthesis in the symAD group. Both share the phenomenon of breaking tight junctions and others. In conclusion, this study offers new understandings of the early biological vicissitudes that occur in the brain before the manifestation of symAD and gives new promising therapeutic targets for early AD intervention.

Keywords: Alzheimer; asymptomatic; genes; microarray; symptomatic.