Select any condition or disease in which you are interested to conduct research study
1. Write two paragraph background, first paragraph describing the disease and second paragraph the gap in literature that you want to address – 1 marks
2. Design research question and develop research hypothesis for the study– 2 marks
3. Describe the study approach and study design you will use to test your hypothesis in one paragraph? – 2 marks
References should be written in APA format
Alzheimer’s disease:
Introduction
Alzheimer’s disease is a progressive neurological disorder that causes the brain and its ability to think to slowly degenerate over time. It is the most common cause of dementia among older adults. The disease is named after Dr. Alois Alzheimer, who first described it in 1906 after examining brain tissue of a deceased patient who had exhibited unusual mental symptoms before her death (Alzheimer’s Association, 2023).
Alzheimer’s disease primarily affects areas of the brain that control thought, memory, and language. As neurons in these regions die, it becomes progressively more difficult for those with Alzheimer’s to remember new information, think clearly, communicate with others, and carry out daily activities. Eventually, patients may lose the ability to carry on a conversation and respond to their environment, leading to a complete loss of personal awareness and independence (Alzheimer’s Association, 2023).
While Alzheimer’s disease was first identified over 100 years ago, there are still many unanswered questions about what causes it and how to effectively treat or prevent it. Current drug therapies can temporarily slow the worsening of symptoms for some patients but do not cure or alter the eventual outcome of the disease. There remains an urgent need for further research to better understand the biological mechanisms underlying Alzheimer’s and identify new targets for therapeutic intervention.
Literature Gap
One area that has received relatively little attention is the potential role of epigenetic changes in Alzheimer’s disease pathogenesis. Epigenetics refers to modifications in gene expression that occur independently of alterations to the underlying DNA sequence. These include DNA methylation, histone modifications, and microRNA regulation—all of which can turn genes on or off without changing the actual DNA code (Mastroeni et al., 2011).
Emerging evidence suggests epigenetic alterations may contribute to Alzheimer’s disease in several key ways. First, epigenetic dysregulation could impact the expression of genes involved in amyloid beta and tau protein production/clearance, which are the primary drivers of neurodegeneration in Alzheimer’s (Mastroeni et al., 2011). Second, epigenetic changes have been linked to aging and age-related diseases, and advancing age is the greatest risk factor for developing Alzheimer’s (Horvath, 2013). Third, environmental exposures and lifestyle factors that influence Alzheimer’s risk, such as diet, exercise levels, and stress, can induce epigenetic modifications (Chouliaras et al., 2013).
Despite these potential connections, relatively few studies have comprehensively profiled epigenetic changes in Alzheimer’s patient brains or explored how epigenetics may interact with genetic and environmental risk factors over the course of the disease. Filling this gap in knowledge could provide novel insights into Alzheimer’s disease pathogenesis and point to new targets for prevention or treatment.
Research Question and Hypothesis
To address this literature gap, the following research question will be explored:
How do DNA methylation patterns differ between the brains of Alzheimer’s patients and cognitively normal controls, and are these epigenetic alterations associated with disease severity or progression?
The hypothesis is that distinct DNA methylation signatures will be observed in Alzheimer’s patient brains compared to controls, and specific epigenetic changes will correlate with worsening clinical symptoms and neuropathological markers of disease progression.
Study Approach and Design
A case-control study design will be used to test this hypothesis. Post-mortem brain tissue samples will be obtained from the hippocampus and frontal cortex of 20 patients who had Alzheimer’s disease and 20 age-matched controls without cognitive impairment. DNA will be extracted from these samples and subjected to genome-wide methylation profiling using Illumina Infinium MethylationEPIC BeadChip arrays, which interrogate over 850,000 CpG sites across the genome.
Methylation levels at each CpG will be compared between Alzheimer’s cases and controls using linear regression models adjusted for age, sex, and other relevant covariates. Sites exhibiting significant differential methylation will be identified. Additionally, methylation levels at sites associated with Alzheimer’s risk genes or pathways will be specifically analyzed. Correlations between methylation and quantitative measures of disease severity, such as Braak staging scores or amyloid plaque/neurofibrillary tangle load, will also be assessed.
Results of this study could provide novel insights into epigenetic alterations involved in Alzheimer’s disease pathogenesis. Sites exhibiting case-control differences or correlations with disease progression may point to epigenetically-regulated genes and pathways meriting further exploration as potential therapeutic targets or biomarkers.
References
Alzheimer’s Association. (2023). What is Alzheimer’s? Retrieved from https://www.alz.org/alzheimers-dementia/what-is-alzheimers
Chouliaras, L., van den Hove, D. L., Kenis, G., Lemmens, M. A., van Os, J., Rutten, B. P., & Steinbusch, H. W. (2013). Epigenetic regulation in the pathophysiology of depression. Progress in neuro-psychopharmacology & biological psychiatry, 42, 85–105. https://doi.org/10.1016/j.pnpbp.2011.12.014
Horvath, S. (2013). DNA methylation age of human tissues and cell types. Genome biology, 14(10), R115. https://doi.org/10.1186/gb-2013-14-10-r115
Mastroeni, D., McKee, A., Grover, A., Rogers, J., & Coleman, P. D. (2011). Epigenetic differences in cortical neurons from a pair of monozygotic twins discordant for Alzheimer’s disease. PloS one, 6(5), e18517. https://doi.org/10.1371/journal.pone.0018517
