Brain diseases like Alzheimer’s pose some of the biggest challenges in medical research today, with few treatment options and an urgent need for new solutions. Scientists have long studied how metabolism, the process by which the body converts food into energy, affects brain health. New research now suggests that a natural compound produced by the body might play a key role in protecting the brain.
Scientists , led by Dr. John Newman, from the Buck Institute for Research on Aging, along with researchers from the Leonard Davis School of Gerontology at the University of Southern California and the University of California, San Francisco, have identified beta-hydroxybutyrate, a type of ketone body produced when the body burns fat for energy. They found it to be a crucial factor in maintaining protein balance in the aging brain and in those with Alzheimer’s disease. Their findings, published in the journal Cell Chemical Biology, highlight how this molecule may help prevent harmful protein buildup linked to brain decline.
Dr. Newman’s team’s found that beta-hydroxybutyrate affects how proteins behave in the brain, particularly those that tend to misfold, meaning they fold into the wrong shape and become dysfunctional. These misfolded proteins accumulate in Alzheimer’s disease. Experiments showed that beta-hydroxybutyrate reduced the toxic effects of amyloid-beta proteins, which are known to form plaques in the brains of Alzheimer’s patients. This was observed in lab-grown cells and tiny worm models often used in scientific studies. More impressively, when older mice were given ketone supplements that increased their beta-hydroxybutyrate levels, their brains showed a reduction in harmful protein clusters. This suggests that beta-hydroxybutyrate may help remove these damaging proteins through a natural biological process that does not rely on changes in acidity, chemical alterations, or other factors.
“Our research shows that beta-hydroxybutyrate interacts with misfolded proteins and helps clear them from the brain,” said Dr. Newman. “This may be a natural way the body protects itself during times of metabolic stress, which occurs when cells struggle to get enough energy.”
Scientists have long known that ketone bodies, including beta-hydroxybutyrate, serve as an alternative energy source when the body has low glucose levels, such as during fasting or a ketogenic diet, a high-fat, low-carbohydrate eating plan. This study suggests that the body may also use beta-hydroxybutyrate to keep harmful protein buildup in check, which could explain why ketogenic diets have been linked to improved brain function and longer lifespans in animals.
These findings open the door to new treatment possibilities for brain diseases. The researchers believe that medications or supplements could be developed to mimic the effects of ketosis, the metabolic state in which the body burns fat instead of carbohydrates for energy. This could potentially offer new options for older adults and those with Alzheimer’s disease.
“Exploring how metabolism affects protein stability, or how well proteins maintain their correct structure and function, is an important step toward developing better treatments for brain disorders,” said Dr. Newman. “Our results suggest that beta-hydroxybutyrate does more than provide energy—it may actively help protect the brain from harmful protein buildup.”
The role of beta-hydroxybutyrate in controlling protein behavior could pave the way for new approaches to treating Alzheimer’s disease and slowing age-related cognitive decline. Future research will focus on translating these findings into therapies that can be tested in clinical settings to determine their effectiveness in humans.
Journal Reference
Madhavan S.S., Roa Diaz S., Peralta S., et al. “Beta-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain.” Cell Chemical Biology, 2025. DOI: https://doi.org/10.1016/j.chembiol.2024.11.001
About the Author
Dr. John Newman is a physician-scientist specializing in aging and metabolism research. He is a faculty member at the Buck Institute for Research on Aging and a practicing geriatrician at the University of California, San Francisco. His research focuses on how metabolic processes, particularly ketone bodies like beta-hydroxybutyrate, influence aging and neurodegenerative diseases such as Alzheimer’s. Dr. Newman explores the potential of dietary and pharmacological approaches to improve brain health and longevity. His work combines laboratory research with clinical applications, aiming to develop therapies that support healthy aging. As a dedicated advocate for translating scientific discoveries into real-world health solutions, he has contributed to numerous peer-reviewed publications and is actively involved in mentoring the next generation of researchers. His groundbreaking studies continue to shape the future of aging science and metabolic health.
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