This series features winners of the Healthy Longevity Global Competition, founded by the National Academy of Medicine, to extend the human health span by accelerating research, innovation, and entrepreneurism in healthy longevity. Agencia Nacional de Investigación y Desarrollo de Chile (ANID) (the National Agency of Research and Development of Chile) funded the project featured in this story.
Innovative Solutions to Advance Healthy Longevity
More than 55 million people worldwide have dementia, with nearly 10 million new cases diagnosed every year, according to the World Health Organization. Dementia—comprising several diseases that affect memory, thinking, and the ability to perform daily tasks—is currently the seventh leading cause of death and one of the major causes of disability among older people.
Dementia places an enormous burden on those affected, their families, health care systems, and even our economies, and there is no cure for these degenerative diseases. Tackling a problem as big as dementia may seem daunting, but bold and innovative research can help bring new treatments, preventative strategies, diagnostics, and other interventions to light.
That is what the team at Universidad Adolfo Ibáñez BrainLat Institute, led by Dr. Carolina Ochoa-Rosales and Dr. Hieab Adams, is working toward. Ochoa-Rosales, a 2023 Healthy Longevity Catalyst Award winner, is discovering novel biomarkers to identify degeneration in specific brain regions, based on chemical changes in someone’s DNA. These changes can be caused by environmental factors and can make earlier diagnosis of neurodegenerative diseases like Alzheimer’s possible. The team’s work has the potential to help prevent disease progression and improve quality of life for patients and caregivers.
The chemical changes Ochoa-Rosales is investigating don’t alter the DNA sequence but can alter how genes are expressed. Identifying DNA fragments in blood plasma that originate from the brain and bear these changes could help medical professionals diagnose Alzheimer’s disease and other dementia-causing neurodegenerative diseases in their early stages, long before a patient begins showing symptoms. These advancements even have the potential to predict a person’s prognosis and monitor disease progression.
Gene-Environment Interactions
Scientists have long believed that without complex gene-editing techniques, human genes go mostly unchanged throughout a person’s lifetime and are passed down to the next generation as-is. But recently, this scientific paradigm was put to the test with the discovery of epigenetics, or the ability for small changes brought on by environmental stimuli to alter the way genes are expressed without changing the DNA’s sequence. The epigenetic breakthrough has led to a new understanding of many diseases and presented new areas of research aimed at identifying these environmentally stimulated changes, understanding how they occur, and determining how we can track them to diagnose conditions earlier to develop new, more powerful treatments and cures.
Researchers have discovered that many different factors can stimulate the way genes are expressed, including a wide range of social and environmental factors. From exposure to air pollution to experiencing discrimination or violence and beyond, research illustrates a correlation between these stimuli and disease prevalence in a population.
Alzheimer’s disease, frontotemporal dementia, and other neurodegenerative diseases are important targets of epigenetic research. These diseases cause molecular changes long before someone ever begins to show symptoms. Currently, there are no accessible, inexpensive methods to track these changes and make early diagnoses that can be critical to improving patients’ lives. This is what Ochoa-Rosales and her team aim to do.
If successful, the improved early diagnosis practices they are working on could benefit patients by not only giving them time to come to terms with their diagnosis while they still have their full-functioning memory, but could even give them a chance to have more years of good health. This would also benefit patients’ families and caregivers who are incredibly invested in the well-being of their loved ones, often taking time out of their own lives to provide crucial care.
“Epigenetic changes can begin to happen in patients with dementia 20 years before they receive an official diagnosis,” said Ochoa-Rosales. “If we are able to identify these changes before patients show symptoms, we may be able to develop strategies to slow down disease progression or even delay its onset.”
Exploring Disease Progression Through Novel Identifiers
While epigenetic research has enormous potential for dementia, traditional methods for identifying epigenetic biomarkers of cell-free fragments of DNA bearing environmentally stimulated chemical changes from a designated part of the body are expensive and difficult to conduct. These methods involve extracting fluid from the brain, spine, or specific cells present in blood. Ochoa-Rosales and her team are looking to apply a cutting-edge technique to find epigenetic biomarkers of dementia that can be easily measured in blood plasma, which is much easier to obtain. This technique was developed to test for certain types of cancers, but Ochoa-Rosales’ project is using the method for neurodegenerative disease for the first time.
“We think that pieces of DNA coming from cells broken by neurodegenerative disorders can leak into the bloodstream,” said Ochoa-Rosales. “These fragments could bear epigenetic patterns that are unique to the brain region associated with diseases that would allow us to see changes that are happening deep in the brain.”
Widespread Impacts and Equity
Not only are Ochoa-Rosales and her team pioneering a new approach to diagnosing neurodegenerative disease, they are also working in unique ways with far-reaching implications for research.
In Latin America, dementia cases are projected to triple by 2050. However, Latin American populations have historically been underrepresented in biomedical research and dementia research in particular. This historical exclusion of Latin American populations in genetic studies has resulted in a lack of knowledge specific to their context and unique environments.
A better understanding of dementia and other neurological disorders rooted in the local context will be crucial to meeting the needs of an aging population and ensuring healthy longevity. Exploratory, innovative projects led by researchers with unique perspectives and experiences, like the project Ochoa-Rosales is leading at The Universidad Adolfo Ibanez BrainLat Institute in Chile, may just be key to unlocking critical new information.
“What’s special about our institute is that we are interested in providing high-quality evidence in Latin American populations because we are underrepresented in all health research, especially in genetics,” said Ochoa-Rosales. “The percentage of Latin American subjects in genetic studies is very small. I wanted to apply my expertise in genetics and epigenetics, which I acquired by studying Caucasian populations, to increase evidence from my own population.”
Learn more about Carolina Ochoa-Rosales, her team, and their project, Identification and Validation of Novel Cell-Free DNA Methylation-Based Biomarkers for Diagnosis of Alzheimer’s Disease and Frontotemporal Dementia and Disease Progression in Blood.
Researchers with project proposals can apply here in January 2025 when the Catalyst Award Application opens. To learn more about the NAM’s Catalyst Awardees, check out these stories. For more information about the Healthy Longevity Global Competition, click here. We appreciate your support in advancing innovative solutions to promote health throughout the human lifespan. Email healthylongevity@nas.edu for questions about the award.