Differential Transcriptome Profiling Unveils Novel Deregulated Gene Signatures Involved in Pathogenesis of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by a progressive loss of cognitive functions at a higher level than normal aging. Although the apolipoprotein (APOE) gene is a major risk factor in developing AD, other genes have also been reported to be linked with complex phenotypes. Therefore, this genome-wide expression study explored differentially expressed genes as possible novel biomarkers involved in AD. The mRNA expression dataset, GSE28146, containing 15 sample data composed of 8 AD cases from the hippocampus region with age-matched control (n = 7, >65 years), was analyzed. Using “affy” R-package, mRNA expression was calculated, while pathway enrichment analysis was performed to determine related biological processes. Of 58 differentially expressed genes, 44 downregulated and 14 upregulated genes were found to be significantly (p < 0.001) altered. The pathway enrichment analysis revealed two altered genes, i.e., dynein light chain 1 (DYNLL1) and kalirin (KLRN), associated with AD in the elderly population. The majority of genes were associated with retrograde endocannabinoid as well as vascular endothelial growth factors affecting the complex phenotypes. The DYNLL1 and KLRN genes may be involved with AD and Huntington’s disease (HD) phenotypes and represent a common genetic basis of these diseases. However, the hallmark of AD is dementia, while the classic motor sign of HD includes chorea. Our data warrant further investigation to identify the role of these genes in disease pathogenesis.

A TMT-based quantitative proteomics approach toward α-syn PFF associated Lewy Body Dementia (LBD) using α-syn PFF-injected mouse brain tissues

“…Investigating the range of varying gene expression levels through mass spectrometry analysis, we have identified several genes which were commonly altered at all time points after α-syn PFF injection, including TPPP3 and RAB10, which were upregulated, and CAMK2A and DYNLL1, which were downregulated. These results agree with prior reports on neurodegenerative diseases, where all four genes displaying association with not only Parkinson’s (Simunovic et al, 2009; Zhang et al, 2014; Olah et al, 2020; Fellgett et al, 2021), but also with Alzheimer’s (Kong et al, 2009; Ghosh and Giese, 2015; Ridge et al, 2017; Singh et al, 2022) disease. Thus, while we may conclude that these genes may serve as potential biomarkers for early detection of general neurodegeneration, it appears difficult to assign them to a particular diagnosis.…”

Exploring the interaction between T-cell antigen receptor-related genes and MAPT or ACHE using integrated bioinformatics analysis

“…Numerous studies have been conducted on NGS public sequencing data of AD. Himanshu Narayan Singh used NGS bioinformatics analysis to determine that DYNLL1 and KLRN were significantly associated with AD, which suggested that these proteins may constitute the genetic basis of AD ( 13 ). Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses performed by Fang indicated that certain functions, such as taxis and cell-cell signaling, were strongly associated with AD ( 14 ).…”