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Alzheimer’s disease is a metabolic disorder of the brain, impairing the ability to metabolize glucose while maintaining the ability to metabolize ketones

Nearly six million individuals live with Alzheimer’s disease (AD) in the U.S., and the numbers continue to rise. After 30 years of encountering dead ends while addressing AD as a problem of brain plaques, researchers are looking at other contributing factors.

New research out of Brigham Young University substantiates a growing body of evidence indicating a strong correlation between AD and a disrupted metabolic state, where the brain can’t get enough energy.

“Alzheimer’s disease is partly a disorder of the brain ‘going hungry’ because it can’t use enough glucose to meet its energy needs,” said senior researcher Dr. Benjamin Bikman, professor of physiology and developmental biology. “Interestingly, these Alzheimer’s brains appear to nevertheless be able to use a different fuel called ketones. As the brain is lacking energy from its inability to properly use glucose, the alternative fuel from ketones becomes increasingly important.”

The research findings prove that the glycolytic and ketolytic metabolism regions of the brain are affected by AD and could be alleviated by ketolysis to fuel glycolytic dysfunctional neurons. The study is published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association.

“There is currently no cure for Alzheimer’s disease, and effective treatment options are limited,” said lead researcher and graduate student Erin Saito. “Hopefully, this research can be translated into clinical practice, in which ketones, ketogenic diets, can be used in both Alzheimer’s disease management and also in disease prevention.”

Dr. Bikman hopes the research findings will motivate people to focus on their metabolic health earlier in life, thus preventing cognitive decline. Preventative measures would include incorporating a diet that keeps the hormone insulin under control. Bikman acknowledged that the standard diet recommended by health professionals promotes carbohydrates—the main insulin-spiking nutrient—as the most significant portion of daily caloric intake.

"I recommend a diet that controls carbohydrates, focusing largely on fruits and vegetables, with refined starches and sugars being a very small contributor," Dr. Bikman said. “Additionally, keeping insulin low for longer periods of time (16+hours) results in the production of ketones. Based on this research and work from other labs, the brain with Alzheimer’s disease can much more readily use ketones, not glucose, as a fuel. These findings of altered metabolic gene expression provide a molecular foundation for the growing number of clinical trials showing an improvement in Alzheimer’s disease with ketones.”

Research contributors include Erin R. Saito, Justin B. Miller, Oscar Harari, Carlos Cruchaga, Kathie A. Mihindukulasuriya, John S. K. Kauwe, and Benjamin T. Bikman. This work was supported by grants from the National Institutes of Health, and the BrightFocus Foundation. Postmortem brain cells and RNA-sequencing data used in the research study were borrowed from the Knight Alzheimer’s Disease Research Center, Mount Sinai Brain Bank, and the Mayo Clinic Brain Bank.