Our genes alone do not determine our chances of developing Alzheimer’s disease, study finds.
Our genes determine many of our physical characteristics such as the colour of our eyes. However, the role of genes in the development of various diseases such as cardiovascular disease, diabetes, neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, is an on-going focus of research. Additionally, a recent study indicates that our genetic code is not the sole determinant of developing Alzheimer’s disease.
In a first of its kind study carried out amongst octogenarian and genetically identical triplets, researchers found that despite sharing the same genes, just two of the three siblings developed Alzheimer’s disease, while one out of the three showed no signs of the disease or mental decline. The two siblings with Alzheimer’s disease were diagnosed in their mid-seventies while the unaffected sibling was still active with normal cognitive functions and day-to-day living. A child of one of the affected siblings was also diagnosed with early-onset Alzheimer’s disease at fifty years of age. This study was published in the December issue of the journal Brain.
The medical history of the triplets showed that all three of them suffered from high blood pressure and the two affected siblings also showed signs of long-standing obsessive-compulsive disorder. Genetic analyses confirmed the identical genetic makeup of the three siblings. The development of late-onset Alzheimer’s disease in two of the siblings could be linked to the presence of a variant of the APOE4 gene, which has been linked to a higher risk of Alzheimer’s disease. Genetic analyses could not explain the development of early-onset Alzheimer’s in the child.
Other factors such as environmental factors could result in epigenetic changes, meaning the gene itself is unchanged but the expression of the gene is affected. One such epigenetic change is the methylation of DNA in certain regions of the genome. The extent of methylation at specific regions of the genome has shown both positive and negative correlations with aging. Aging is one of the biggest risk factors for Alzheimer’s. Scientists calculate the epigenetic age of an individual based on the methylation status of specific regions. A comparison of the epigenetic age with the chronological age of the triplets in this study showed that their epigenetic age was about six to ten years younger than their chronological age. In contrast, the child who developed early-onset Alzheimer’s showed accelerated aging with an epigenetic age that was nine years older than chronological age. This suggests that accelerated epigenetic aging could be correlated with an increased risk of early-onset Alzheimer’s disease. As explained by Dr. Ekaterina Rogaeva, a senior author on the paper, “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 and as a result some cells could mutate and change over time.”
While this study includes a unique dataset of three genetically identical siblings, it is a small dataset. The researchers are looking to improve the study by including their current analyzes in their ongoing whole-genome sequencing Alzheimer’s disease project. Additionally, they are interested in brain imaging studies that include each family member from this study to observe the brain plaques, which are a common sign of Alzheimer’s.
Dr. Morris Freedman, another senior author on the paper and head of neurology at Baycrest Health Sciences, Canada notes that “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, we don’t know what it is, which could either protect against or accelerate dementia.”
Written by Bhavana Achary, Ph.D
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
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