Brain sugar stores linked to Alzheimer’s development
Glucose stored in the brain may play a more active role in driving neuron damage than previously believed, raising new possibilities for treating Alzheimer’s disease.
The research challenges the long-held view that glycogen – the storage form of glucose – is simply a backup energy supply for the liver and muscles.
Instead, scientists have identified interactions between sugar stores and protein build-ups commonly seen in Alzheimer’s that may worsen the condition.
Alzheimer’s is classified as a tauopathy, a disorder marked by the accumulation of tau proteins inside brain cells.
Whether this build-up causes the disease or is a symptom of it remains uncertain, but the new study adds to evidence that sugar storage may intensify the damage.
Researchers from the Buck Institute for Research on Aging in the US found unusually high levels of glycogen in fruit fly (Drosophila melanogaster) models of tauopathy and in human brain cells from people with Alzheimer’s.
Molecular biologist Pankaj Kapahi from the Buck Institute said: “This new study challenges that view, and it does so with striking implications.
“Stored glycogen doesn’t just sit there in the brain, it is involved in pathology.”
The team showed that tau proteins interfere with normal glycogen breakdown in brain cells, disrupting energy balance, lowering protective neuron defence mechanisms and creating a cycle in which both tau and glycogen accumulate to harmful levels.
At the centre of this process is glycogen phosphorylase (GlyP), an enzyme that helps convert stored glycogen into usable energy.
When the researchers increased GlyP activity in fruit flies with tauopathy, the brain was better able to manage sugar stores and reduce stress.
Buck Institute biologist Sudipta Bar said: “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.”
The researchers also tested the impact of dietary restriction, which is already associated with better brain function.
Flies fed a low-protein diet lived longer and showed fewer signs of brain damage, suggesting that dietary changes may support better sugar metabolism in the brain.
To mimic this effect without altering diet, the team developed a compound based on 8-Br-cAMP. In tests on fruit flies, the compound offered similar benefits, indicating it may activate the same protective pathways as dietary restriction.
The findings may help explain why drugs like GLP-1 receptor agonists – including Ozempic, which is used for diabetes and weight loss – have shown potential in dementia research.
The team suggests these drugs might influence glycogen-related processes in the brain.
Kapahi said: “By discovering how neurons manage sugar, we may have unearthed a novel therapeutic strategy: one that targets the cell’s inner chemistry to fight age-related decline.
“As we continue to age as a society, findings like these offer hope that better understanding – and perhaps rebalancing – our brain’s hidden sugar code could unlock powerful tools for combating dementia.”
