Epigenetics and Alzheimer’s Disease
- 1 day ago
- 5 min read
Written by: Deepika Miryala
Edited by: Fahad Hassan Shah and Nadia Hall
Abstract
Currently, Alzheimer's disease is one of the leading causes of death globally. For years, scientists have considered genetics to be one of the most important areas of study when it comes to the human body and lifespan. In recent years, a relatively new area of interest known as epigenetics has gained recognition. Epigenetics deals with the subtle changes that occur to the human genome throughout an individual’s lifetime, as caused by lifestyle choices and environmental factors. Connections have been found between epigenetics and Alzheimer’s disease, leading scientists to investigate the epigenetic causes and solutions to this disorder. So far, multiple genetic alterations have been identified, as well as their epigenetic roots. While epigenetics can have unfavorable effects on the human genome, people can also adopt lifestyle changes that produce favorable results. Combining these changes with innovative medications that target the epigenome could lead to the next great advancement in the fight against Alzheimer’s.
Introduction to Alzheimer’s
Alzheimer’s disease is the world’s most common form of dementia. It is a neurodegenerative disorder that is the result of nerve damage in the brain (CDC, 2024). The cognitive impairment associated with it is primarily characterized by memory failure, specifically short-term memory loss that is distinguished by an inability to recall recent memories (National Institute on Aging, 2023; Qazi et al., 2018). Additionally, it can cause “deficits in executive, language, and/or visuospatial functions, behavioral changes, and consequently death” (Perkovic et al., 2021). It is a progressive disease, meaning the symptoms worsen over time, and sadly, it is currently listed as the seventh most common cause of death in the United States (CDC, 2024; National Institute on Aging, 2023).
Pathologically speaking, Alzheimer’s disease is the result of “extraneuronal amyloid plaque (Aβ) deposition and intracellular neurofibrillary tangles (NFTs)” (Gao et al., 2022). The devastating effects of this illness have prompted experts to search diligently for its causes and potential remedies.
What is Epigenetics?
Epigenetics is a field of genetics that studies how gene activity is controlled and changed without changing the DNA sequence itself (MedlinePlus, 2021). It is considered to be the intersection of genetics and developmental biology (Gao et al., 2022). The epigenome can affect things such as metabolism, cancer development, intellectual disabilities, autoimmune diseases, and a range of other physiological conditions (Cleveland Clinic, 2024). Some prominent factors that can shape the epigenome include childhood trauma, diet, exercise, relationships, and exposure to toxins (Cleveland Clinic, 2024). Essentially, epigenetics determines whether genes are turned on or off (MedlinePlus, 2021).
Some major epigenetic mechanisms include histone modification, DNA methylation, and non-coding RNAs (Qazi et al., 2018), with the most prominently researched epigenetic factor regarding Alzheimer’s being DNA methylation (Koulouri & Zannas, 2024). DNA methylation is when chemical groups known as methyl groups attach to nucleotides, turning that gene off and preventing protein synthesis from occurring with it (Gao et al., 2022). Specifically, a methyl group is attached to the fifth atom of a cytosine base. This impairs transcription of the affected gene by preventing transcription factors from binding to promoters, modifying chromatin structure to make it inaccessible, and more. (Gao et al., 2022).
How Does Epigenetics Affect Alzheimer’s?
Some epigenetic factors that pertain to neurodegeneration include DNA methylation, histone acetylation, and microRNAs, though there are several more (Koulouri & Zannas, 2024). Recent research has shown strong connections between epigenetics and Alzheimer’s disease, specifically regarding DNA methylation (Perkovic et al., 2021). Some studies have revealed that cytosine methylation in the human genome is reduced as a person grows older, especially in Alzheimer’s patients, proving the correlation between the disease and the epigenome (Qazi et al., 2018).
While there are a plethora of hypotheses analyzing which specific genes are implicated, one notable example is the tau hypothesis, which posits that irregular methylation patterns cause downregulation of a certain polypeptide known as the tau protein and inhibit its transcription (Qazi et al., 2018). Basically, these alterations hamper synaptic plasticity and damage memory-related gene function (Gao et al., 2022). The factors influencing these modifications of the epigenome can include a diet that lacks fundamental nutrients, limited exercise, and social isolation/loneliness (National Institute on Aging, 2023). In addition, epigenetic biomarkers of the disease have been located in the blood and human cerebrospinal fluid (Perkovic et al., 2021).
Strategies to Prevent Alzheimer’s
Knowing that the epigenome can change, individuals can take steps to alter their epigenetics and produce positive changes. For one, maintaining a healthy diet is vital, especially in regard to proper nutrition. Calorie restriction has been shown to have neuroprotective effects against Alzheimer’s, namely by employing histone deacetylases, which provide benefits such as boosting mitochondrial performance levels and mitigating oxidative stress (Koulouri & Zannas, 2024). Overall, the benefits of a well-thought-out diet significantly influence the brain’s resilience against aging, and nutrition is a key player in staving off neurodegenerative disease.
Regulating lifestyle choices such as smoking and psychological stress are also important to reduce the risk of developing neurodegenerative maladies (Villa & Combi, 2024). Similarly, maintaining a healthy exercise routine and cultivating a positive relationship with stress are key to sustaining cognitive abilities. In terms of medicinal implications, histone deacetylase inhibitors (HDACi) can offset the genetic effects of Alzheimer’s, including tau protein phosphorylation, Aβ accumulation, and poor synaptic plasticity (Perkovic et al., 2021). Further, it can aid in memory consolidation and learning capabilities (Perkovic et al., 2021).
Conclusion
Alzheimer’s disease is prevalent in the modern world, and researchers have made it a goal to understand its causes, effects, and possible solutions. In order to do this, it is necessary to have a comprehensive understanding of the biological mechanisms that underlie the disease. These mechanisms encompass the field of epigenetics, and with a thorough investigation of the link between the epigenome and neurodegeneration, it may help us get closer to finding more effective treatments.
References
CDC. (2024, August 15). About Alzheimer's. Alzheimer's Disease and Dementia. https://www.cdc.gov/alzheimers-dementia/about/alzheimers.html
Cleveland Clinic. (2024, February 16). What Is Epigenetics? Cleveland Clinic. https://my.clevelandclinic.org/health/articles/epigenetics
Gao, X., Chen, Q., Yao, H., Tan, J., Liu, Z., Zhou, Y., & Zou, Z. (2022). Epigenetics in Alzheimer's disease. Frontiers in aging neuroscience, 14, 911635.
Koulouri, A., & Zannas, A. S. (2024). Epigenetics as a link between environmental factors and dementia risk. Journal of Alzheimer's Disease Reports, 8(1), 1372-1380.
MedlinePlus. (2021, June 11). What is Epigenetics? Medlineplus.gov; National Library of Medicine. https://medlineplus.gov/genetics/understanding/howgeneswork/epigenome/
National Institute on Aging. (2023, April 5). Alzheimer's Disease Fact Sheet. National Institute on Aging; National Institutes of Health. https://www.nia.nih.gov/health/alzheimers-and-dementia/alzheimers-disease-fact-sheet
Perkovic, M., N., Paska, A., V., Konjevod, M., Kouter, K., Strac, D., S., Erjavec, G., N., & Pivac, N. (2021). Epigenetics of Alzheimer's disease. Biomolecules, 11(2), 195.
Qazi, T. J., Quan, Z., Mir, A., & Qing, H. (2018). Epigenetics in Alzheimer's disease: perspective of DNA methylation. Molecular Neurobiology, 55, 1026-1044.
Role of DNA methylation in disease. labclinicscom. (n.d.). https://www.labclinics.com/2018/11/08/role-dna-methylation-disease/?lang=en
Villa, C., & Combi, R. (2024). Epigenetics in Alzheimer's disease: a critical overview. International Journal of Molecular Sciences, 25(11), 5970.