Identification of Genes Associated with Alzheimer’s Disease in Thailand Using RNA Sequencing Analysis
Conference proceedings article
ผู้เขียน/บรรณาธิการ
กลุ่มสาขาการวิจัยเชิงกลยุทธ์
รายละเอียดสำหรับงานพิมพ์
รายชื่อผู้แต่ง: Monwipha Milintawisamai, Nongluk Plongthongkum, Chinae Thammarongtham, Supatcha Lertampaiporn, Supapon Cheevadhanarak, and Weerayuth Kittichitirat
ปีที่เผยแพร่ (ค.ศ.): 2024
บทคัดย่อ
Dementia is a syndrome characterized by progressive decline of cognitive function. As a result, patients loss the abilities to perform basic activities in daily life. Alzheimer’s disease (AD) is the most common cause of dementia, which contributes up to 80% of all dementia diagnose [1]. There are 50 million AD patients worldwide and this number will increase to 152 million in 2050 [2]. National Institute on Aging-Alzheimer’s Association (NIA-AA) classified AD continuum into 5 stages including preclinical AD, AD with mild cognitive impairment (MCI), AD with mild dementia, AD with moderate dementia, and AD with severe dementia [3]. Currently, drugs for AD patients are effective only in treating the symptoms of AD. Thus, there is still no drug for curing and preventing of AD [2]. Early diagnosis is important to delay the progression of AD, which can be beneficial to patients, their carers and healthcare systems [4].
AD is characterized by the accumulation of amyloid-beta peptide (Aβ) and Tau protein. The Aβ is generated by cleavage of the transmembrane APP. When monomers of Aβ become oligomer, it will lead to plaques formation. The accumulation of Aβ in the intraneuronal leads to neurotoxic processes. Aβ also plays a role in inducing Tau hyperphosphorylation, which lead to the formation of protein tangles. The accumulation of hyperphosphorylated Tau in neurons lead to protein misfold and aggregation in intracellular neurofibrillary tangles (NFT), which reducing their affinity for microtubules. This results in a disturbance in the structural and regulatory functions of the cytoskeleton in neuronal cells. In addition, other pathological paths play important roles in AD development as well. For instance, neuroinflammation, oxidative stress and autophagy dysregulation [5]. However, the molecular mechanism that contributes to AD is still unclear. Understanding the molecular mechanisms in AD can help us to develop early diagnosis and therapeutic drug, which can delay progression of AD.
High-throughput sequencing technology and bioinformatic tools offer invaluable assistance in the study complex diseased. Transcriptome analysis has been used for studying gene-expression alterations, non-coding RNAs, copy number variants (CNVs), or alternative splicing [6]. The analysis can provide insights into biological pathways and molecular mechanisms of AD. Workflow for transcriptome analysis consist of five steps including preprocessing, read alignment, transcriptome reconstruction, expression quantification and differential expression analysis [7]. Differential expression analysis aims to identify differentially expressed genes (DEGs). Many studies used differential expression analysis to quantify gene expression between biological samples in difference conditions. By using this analysis, the relative expression level of genes can be obtained. Subsequently, the gene expression will be used for statistical tests [8] for finding the important genes that may play important role in AD.
In Thailand, the number of elderly populations is increasing. It was estimated that there will be more than a million people with dementia in 2030 and 2 million in 2050 [9], consistent with the global trend [2]. However, there is still lack of knowledge of AD specific genes for Thai patients. This information can be used for studying biological mechanisms underlying AD. In this study, transcriptome analysis was conducted to pinpoint the genes that specifically contribute to AD. Expressed transcripts in AD patients and healthy controls were identified and quantified. Consequently differential expressed transcripts between AD patients and healthy controls can be obtained. The results of this study help us understand function of significant differentially expressed transcripts, which will help to gain insight into pathogenesis mechanism of AD. In addition, they can reveal genes that may play an important role in AD that are specific to Thai AD patients.
คำสำคัญ
ไม่พบข้อมูลที่เกี่ยวข้อง