A new study from the University of California, Irvine suggests that a combination of two widely available compounds—a form of vitamin B3 and an antioxidant found in green tea—could help aging brain cells clean house and fight off the protein buildup associated with Alzheimer’s disease.
In lab-grown neurons from aged and genetically predisposed mice, the treatment restored energy levels and triggered the cells’ natural waste disposal system, clearing toxic protein clumps in just 24 hours. The findings, published August 2 in GeroScience, could open a new path toward dietary or nonpharmaceutical interventions for neurodegenerative disease.
Boosting Brain Energy to Power Cleanup
As we age, neurons lose energy. This slows down critical processes like autophagy, the brain’s way of recycling damaged components. The new study focuses on guanosine triphosphate (GTP), a lesser-known energy molecule essential for driving autophagy and cellular trafficking. Using a fluorescent biosensor called GEVAL, the researchers tracked GTP levels in real time inside neurons taken from aging Alzheimer’s model mice.
They found that GTP levels dropped dramatically with age—especially in the mitochondria, the cell’s energy factories. This energy loss impaired the ability of neurons to remove toxic amyloid-beta (Aβ) aggregates, a key feature of Alzheimer’s pathology.
Then came the turnaround:
- A 24-hour treatment with nicotinamide (a form of vitamin B3) and EGCG (a green tea compound) fully restored GTP levels in aged neurons
- Autophagy markers improved, and cellular “cleanup crews” mobilized
- Aβ protein clumps and signs of oxidative stress were sharply reduced
“We found that restoring energy levels helps neurons regain this critical cleanup function,” said Gregory Brewer, adjunct professor of biomedical engineering at UC Irvine and lead author of the study.
One-Two Punch: Energy and Redox Balance
The treatment worked because it attacked the problem from two sides: energy production and redox balance. Nicotinamide boosts the brain’s supply of NAD+, a molecule critical for mitochondrial function and GTP generation. EGCG, on the other hand, activates Nrf2, a transcription factor that turns on genes protecting cells from oxidative stress.
When combined, these compounds jump-started the cell’s internal recycling system. Specifically, they improved the activity of two small GTPases—Rab7 and Arl8b—that help shuttle waste-filled vesicles through the neuron. Without enough GTP, these systems stall and accumulate junk. With the treatment, vesicle traffic resumed, and Aβ levels declined.
Alzheimer’s Risk and the Role of Autophagy
Age is the biggest risk factor for Alzheimer’s disease. But scientists are still working to understand how aging increases that risk. This study adds a key piece to the puzzle: GTP levels fall with age, leading to stalled autophagy and buildup of harmful proteins.
“This study highlights GTP as a previously underappreciated energy source driving vital brain functions,” Brewer noted.
In the Alzheimer’s-prone mouse neurons, GTP loss started even earlier—at middle age—suggesting a compounding effect of genetic risk and aging. The combined treatment rescued both age-related and Alzheimer’s-related declines, at least in a dish.
Why Not Just Take Supplements?
Before you start stocking up on green tea extract and B3 pills, there’s a catch. Brewer pointed out that in a recent clinical trial, oral nicotinamide didn’t work well because it gets inactivated in the bloodstream. Finding an effective way to deliver these compounds to the brain remains a challenge.
Still, the implications are promising. These compounds are already available as dietary supplements, and the rapid effects seen in this study suggest that the right formulation could have therapeutic potential—not just for neurons, but possibly for glial, vascular, and immune cells as well.
Looking Ahead
The team plans to explore in vivo models to test cognitive improvements and determine optimal dosing strategies. Meanwhile, the findings offer a new lens on brain aging: it’s not just about plaque accumulation, but also about a quiet energy crisis that stalls the brain’s natural cleanup systems.
“By supplementing the brain’s energy systems with compounds that are already available as dietary supplements, we may have a new path toward treating age-related cognitive decline and Alzheimer’s disease,” Brewer said.
Journal: GeroScience
DOI: 10.1007/s11357-025-01204-5
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