Integrated Transcriptomics and Network Analysis Identified Altered Neural Mechanisms in Frontal Aging Brain-Associated Alzheimer's Disease

Biochem Genet. 2023 Nov 7. doi: 10.1007/s10528-023-10549-9. Online ahead of print.

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease. The late stage of AD typically develops after 60 years of age and AD pathogenesis can be detected predominately in the frontal lobe, which is responsible for memory. Multiple alterations in cellular mechanisms have been associated with AD, but there is no clear information on AD pathogenesis during brain aging. This study aimed to explore the differentially expressed genes (DEGs) in the frontal lobe of aging brains and to identify shared crucial mechanisms in the aging brain linked to AD pathogenesis. Three datasets were downloaded from the Gene Expression Omnibus (GEO). Biological function analysis was performed by DAVID and KEGG databases. An AD patient's cohort (GSE150696) was collected for verification of the enriched pathway. The results demonstrated that multiple neurochemical synapsis and regulation of the cytoskeleton are linked to AD pathogenesis during aging. Taken together, this study contributes to our further understanding of neural alterations during aging in AD that could be used to develop therapeutics for early intervention to prevent or slow progression.

Keywords: Aging brain; Alzheimer’s disease; Dopaminergic synapse; Network analysis; Neurodegenerative diseases.