Surprise Discovery Could Rewrite What We Know About Alzheimer’s

A new study just uncovered a surprising link between how brain cells manage sugar and the progression of Alzheimer’s disease—and the implications could reshape future treatments.

Researchers at the Buck Institute for Research on Aging have discovered that stored glucose, in the form of glycogen, may not be the passive energy reserve scientists once assumed. Instead, it may actively contribute to the buildup of tau proteins, a hallmark of Alzheimer’s and other neurodegenerative diseases.

Tauopathies like Alzheimer’s are characterized by toxic tangles of tau inside neurons. But this study, published in Nature Metabolism, found that those tangles may form, at least in part, because of disruptions in how glycogen is processed in the brain.

“Stored glycogen doesn’t just sit there in the brain,” said Buck Institute biologist Pankaj Kapahi. “It is involved in pathology.”

Using fruit fly models and postmortem brain cells from people with Alzheimer’s, scientists found elevated levels of both tau and glycogen. The buildup appeared to be driven by a breakdown in how glycogen is metabolized, specifically through the enzyme glycogen phosphorylase (GlyP), which normally helps convert glycogen into usable fuel.

When researchers increased GlyP activity in the flies, they saw significant benefits. Brain cells reduced oxidative stress, protected themselves better, and even lived longer.

The team also tested whether a low-protein diet, already linked to improved brain health, might produce similar effects. It did. Fruit flies fed this restricted diet showed fewer signs of damage and extended lifespans, suggesting that dietary changes could naturally shift brain metabolism in a protective direction.

Even more intriguing, the researchers developed a drug that mimicked the effect of dietary restriction. It worked. And they noted potential crossover with medications like Ozempic, which may also support brain health by targeting glycogen-related pathways.

“By discovering how neurons manage sugar,” said lead researcher Sudipta Bar, “we may have unearthed a novel therapeutic strategy—one that targets the cell’s inner chemistry to fight age-related decline.”

If future studies replicate these results in humans, this could mark a turning point in our understanding and treatment of Alzheimer’s.

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