Genes and Alzheimer’s Disease: A New Perspective

The Role of Genetics in Disease Development

Our genes play a significant role in determining various physical traits, such as eye color. However, their influence on the development of diseases, including cardiovascular conditions, diabetes, and neurodegenerative disorders like Parkinson’s and Alzheimer’s disease, remains an area of active research. A recent study suggests that genes are not the only factor influencing the likelihood of developing Alzheimer’s disease.

Study of Identical Triplets

In a pioneering study involving octogenarian genetically identical triplets, researchers discovered that despite sharing the same genetic makeup, only two of the three siblings developed Alzheimer’s disease. The third sibling showed no signs of the disease or cognitive decline. The siblings diagnosed with Alzheimer’s were identified in their mid-seventies, while the unaffected sibling maintained normal cognitive functions and an active lifestyle. Additionally, a child of one of the affected siblings was diagnosed with early-onset Alzheimer’s at the age of fifty. This research was published in the December issue of the journal Brain.

Medical History and Genetic Findings

The triplets’ medical history revealed that all three suffered from high blood pressure, and the two affected siblings exhibited long-standing obsessive-compulsive disorder. Genetic analyses confirmed their identical genetic structure. The late-onset Alzheimer’s cases in two siblings may be associated with a variant of the APOE4 gene, known for increasing Alzheimer’s risk. However, the genetic analysis could not elucidate the early-onset Alzheimer’s in the child.

Environmental and Epigenetic Influences

The study highlights the potential impact of environmental factors on gene expression through epigenetic changes. These changes do not alter the underlying DNA but can influence how genes are expressed. One significant epigenetic alteration involves DNA methylation in specific genomic regions, which has demonstrated both positive and negative correlations with aging. Aging is a major risk factor for Alzheimer’s.

Scientists assess an individual’s epigenetic age based on the methylation status of certain genomic regions. In this study, comparisons indicated that the triplets had an epigenetic age six to ten years younger than their chronological age. Conversely, the child with early-onset Alzheimer’s displayed accelerated aging, with an epigenetic age nine years older than their chronological age. This finding suggests a link between accelerated epigenetic aging and a heightened risk of early-onset Alzheimer’s disease.

Insights from Researchers

Dr. Ekaterina Rogaeva, a senior author of the study, explains, “The latest genetics research is finding that the DNA we die with isn’t necessarily what we received as a baby, which could relate to why two of the triplets developed Alzheimer’s and one didn’t. As we age, our DNA ages with us, leading some cells to mutate and change over time.”

Future Research Directions

While this study utilizes a unique dataset of genetically identical siblings, it is limited in size. Researchers aim to enhance their findings by including these analyses in their broader whole-genome sequencing project focused on Alzheimer’s disease. They also plan to conduct brain imaging studies involving each family member to investigate the presence of brain plaques, commonly associated with Alzheimer’s.

Dr. Morris Freedman, another senior author and head of neurology at Baycrest Health Sciences in Canada, emphasizes the implications of the study: “These findings show that your genetic code doesn’t dictate whether you are guaranteed to develop Alzheimer’s. There is hope for people who have a strong family history of dementia since there are other factors, whether it’s the environment or lifestyle, that could either protect against or accelerate dementia.”

Conclusion

This research highlights the complexity of Alzheimer’s disease development, suggesting that genetics is just one piece of the puzzle. Future studies will continue to explore the interplay between genetic, environmental, and lifestyle factors in relation to this challenging condition.

References

Zhang M, Dilliott AA, Khallaf R, Robinson JF, Hegele RA, Comishen M, Sato C, Tosto G, Reitz C, Mayeux R, George-Hyslop PS, Freedman M, Rogaeva E. Genetic and epigenetic study of an Alzheimer’s disease family with monozygotic triplets. Brain. 2019 Nov 1;142(11):3375-3381. News release retrieved from https://www.eurekalert.org/pub_releases/2019-12/bcfg-yga121119.php. Image by Gerd Altmann from Pixabay.