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

Himanshu Narayan Singh,Sanjay Kumar,Niraj Kumar Jha,Anjani Kumar Singh,Vishnu Swarup,Wen-Cheng Lo,Navneet Kumar Dubey

doi:10.3390/biomedicines10030611

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 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.

Highlights

Introduction conditions of the Creative CommonsAlzheimer’s disease (AD; OMIM 104300) is a progressive neurodegenerative disorder and the most frequent cause of dementia in the elderly, with prevalence rising substantially between 65 years and older [1,2]
60–80% of AD is inherited in elderly populations, genetic and environmental factors play a crucial role in the onset, progression, and severity of phenotype [4,5]
The results showed deregulation of DYNLL1 and KLRN in AD (Table 1) [56], which is associated with the Huntington’s disease (HD) phenotypes [57]

Summary

Introduction

Alzheimer’s disease (AD; OMIM 104300) is a progressive neurodegenerative disorder and the most frequent cause of dementia in the elderly, with prevalence rising substantially between 65 years and older [1,2]. Biomedicines 2022, 10, 611 age of 65, with the diagnosis of 1275 new cases/year/100,000 individuals over 65 years, such that 30%–50% of all people become affected by the age of 85 [2,3]. 60–80% of AD is inherited in elderly populations, genetic and environmental factors play a crucial role in the onset, progression, and severity of phenotype [4,5]. AD is developed through the extracellular deposition of amyloid-β (Aβ), senile plaques (SP), loss of synapses, and intracellular formation of neurofibrillary tangles (NFTs), mainly comprising hyper-phosphorylated tau filaments [6].

Methods

Results

Conclusion