Differential Transcriptome Profiling Unveils Novel Deregulated Gene Signatures Involved in Pathogenesis of Alzheimer's Disease.
Himanshu Narayan SinghVishnu SwarupNavneet Kumar DubeyNiraj Kumar JhaAnjani Kumar SinghWen-Cheng LoSanjay KumarPublished in: Biomedicines (2022)
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 7 AD cases from the hippocampus region with age-matched control (n = 8, >80 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.
Keyphrases
- genome wide
- dna methylation
- genome wide identification
- copy number
- bioinformatics analysis
- genome wide analysis
- type diabetes
- machine learning
- gene expression
- single cell
- cognitive decline
- multiple sclerosis
- mild cognitive impairment
- electronic health record
- metabolic syndrome
- adipose tissue
- big data
- poor prognosis
- brain injury
- cognitive impairment
- endothelial cells
- blood brain barrier
- subarachnoid hemorrhage