Brain Sugar Metabolism: A New Target in Alzheimer’s Fight – Could Dietary Restriction & GLP-1 Drugs Hold the Key?
New York, NY – July 1, 2025 – A groundbreaking study published today in Nature Metabolism reveals a surprising link between brain sugar metabolism and Alzheimer’s disease, offering potential new avenues for treatment and prevention. Scientists at the Buck Institute for Research on Aging have discovered that the breakdown of glycogen – a stored form of glucose – within neurons plays a critical role in protecting the brain from the toxic protein buildup characteristic of Alzheimer’s and other forms of dementia.For years, glycogen was considered largely irrelevant in neurons, primarily existing in support cells like astrocytes.This research fundamentally challenges that notion, demonstrating that glycogen isn’t simply stored in the brain, but actively involved in disease pathology.”Stored glycogen doesn’t just sit there in the brain; it is involved in pathology,” explains Professor Pankaj Kapahi, PhD, senior scientist on the study.
The research team, led by postdoc Sudipta Bar, PhD, found that neurons in both fly and human models of tauopathy – a group of neurodegenerative diseases including Alzheimer’s – accumulate excessive glycogen. Crucially, the protein tau, known for forming tangles in the brains of Alzheimer’s patients, appears to bind to glycogen, preventing its breakdown.
This blockage has important consequences.When glycogen can’t be broken down, neurons loose a vital mechanism for managing oxidative stress – a major contributor to aging and neurodegeneration.
Restoring Glycogen Breakdown: A Protective Effect
The team successfully reduced tau-related damage in fruit flies and human stem cell-derived neurons by restoring the activity of glycogen phosphorylase (GlyP), the enzyme responsible for initiating glycogen breakdown.
Instead of using glycogen for energy, these enzyme-boosted neurons channeled sugar molecules into the pentose phosphate pathway (PPP), generating NADPH and Glutathione – powerful antioxidants that combat oxidative stress. “By increasing GlyP activity, the brain cells could better detoxify harmful reactive oxygen species, thereby reducing damage and even extending the lifespan of tauopathy model flies,” says Bar.
Dietary Restriction & GLP-1 Drugs: Promising Avenues
The study also uncovered a compelling connection to lifestyle and existing medications. Dietary restriction (DR), a known lifespan-extending intervention, was shown to naturally enhance GlyP activity and improve outcomes in flies. furthermore, the team successfully mimicked the benefits of DR pharmacologically using a molecule called 8-Br-cAMP, suggesting a potential drug-based approach to activate this sugar-clearing system.
Kapahi notes this research may explain the observed promise of GLP-1 drugs – currently popular for weight loss – in combating dementia. “This work could explain why GLP-1 drugs, now widely used for weight loss, show promise against dementia, potentially by mimicking dietary restriction,” he states.
Implications for Alzheimer’s Research
This research opens exciting new avenues for Alzheimer’s research, shifting focus towards the critical role of brain sugar metabolism.Further examination into GlyP activation and the potential of DR-mimicking drugs could lead to innovative therapies for preventing and treating this devastating disease.
Keywords: Alzheimer’s Disease, Dementia, Glycogen, Tau, Glycogen Phosphoryase, Oxidative Stress, Dietary Restriction, GLP-1 Drugs, Brain Health, Neurodegeneration, Aging, Research, Nature Metabolism.
Call to Action: Learn more about Alzheimer’s disease and current research efforts at the Alzheimer’s Association: https://www.alz.org/
