The battle against Alzheimer’s disease and other forms of dementia has just received a surprise player: brain sugar metabolism. A new study from scientists at the Buck Institute for Research on Aging has revealed that breaking down glycogen – a stored form of glucose – in neurons may protect the brain from toxic protein buildup and degeneration.

Glycogen is typically thought of as a reserve energy source stored in the liver and muscles, but small amounts also exist in the brain. The research team, led by postdoc Sudipta Bar, PhD, discovered that in both fly and human models of tauopathy (a group of neurodegenerative diseases including Alzheimer’s), neurons accumulate excessive glycogen. This buildup appears to contribute to disease progression.

Tau, the infamous protein that clumps into tangles in Alzheimer’s patients, physically binds to glycogen, trapping it and preventing its breakdown. When glycogen can’t be broken down, the neurons lose an essential mechanism for managing oxidative stress, a key feature in aging and neurodegeneration.

By restoring the activity of an enzyme called glycogen phosphorylase (GlyP), which kicks off the process of glycogen breakdown, the researchers found they could reduce tau-related damage in fruit flies and human stem cell-derived neurons. Rather than using glycogen as a fuel for energy production, these enzyme-supported neurons rerouted the sugar molecules into the pentose phosphate pathway (PPP) – a critical route for generating NADPH (nicotinamide adenine dinucleotide phosphate) and Glutathione, molecules that protect against oxidative stress.

The team demonstrated that dietary restriction (DR) naturally enhanced GlyP activity and improved tau-related outcomes in flies. They further mimicked these effects pharmacologically using a molecule called 8-Br-cAMP, showing that the benefits of DR might be reproduced through drug-based activation of this sugar-clearing system.

Researchers also confirmed similar glycogen accumulation and protective effects of GlyP in human neurons derived from patients with frontotemporal dementia (FTD), strengthening the potential for translational therapies. The study emphasizes the power of the fly as a model system in uncovering how metabolic dysregulation impacts neurodegeneration.

The researchers acknowledge the Buck’s highly collaborative atmosphere as a major factor in the work, highlighting the expertise in fly aging and neurodegeneration, proteomics, human iPSCs, and neurodegeneration. The study not only highlights glycogen metabolism as an unexpected hero in the brain but also opens up a new direction in the search for treatments against Alzheimer’s and related diseases.

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.

A recent study by researchers at the Case Western Reserve School of Medicine has made an astonishing discovery that may revolutionize the way we approach dementia prevention. The research team found that semaglutide, a popular medication used to treat diabetes and aid in weight loss, could significantly lower the risk of dementia in people with type 2 diabetes (T2D).

Dementia is a devastating condition that affects millions worldwide, causing memory loss and cognitive decline. It occurs when brain cells are damaged, disrupting their connections and ultimately leading to this debilitating state. Encouragingly, studies indicate that approximately 45% of dementia cases could be prevented by addressing modifiable risk factors.

The study, published in the Journal of Alzheimer’s Disease, analyzed three years’ worth of electronic records from nearly 1.7 million T2D patients nationally. The researchers used a statistical approach that mimicked a randomized clinical trial to determine the effectiveness of semaglutide in preventing dementia.

Their findings suggest that patients prescribed semaglutide had a significantly lower risk of developing Alzheimer’s disease-related dementia compared to those taking other anti-diabetic medications, including GLP-1R-targeting medications. These results were even more pronounced in women and older adults.

Semaglutide, a glucagon-like peptide receptor (GLP-1R) molecule that decreases hunger and regulates blood sugar levels in T2D patients, has shown remarkable benefits beyond its primary use as a diabetes treatment. It also reduces the risk of cardiovascular diseases, further solidifying its potential in preventing dementia.

The study’s lead researcher, biomedical informatics professor Rong Xu, stated, “There is no cure or effective treatment for dementia, so this new study provides real-world evidence for its potential impact on preventing or slowing dementia development among at-high risk populations.”

While the findings are promising, it’s essential to note that further research through randomized clinical trials will be necessary to confirm the causal relationship between semaglutide and dementia prevention. Nevertheless, this groundbreaking study offers a glimmer of hope in the quest to combat dementia and improve the lives of millions worldwide.

The common blood test known as the triglyceride-glucose (TyG) index has long been used to detect insulin resistance. New research presented at the European Academy of Neurology Congress 2025 suggests that this simple test could also be used to predict how fast Alzheimer’s disease progresses in individuals with mild cognitive impairment.

A team of neurologists from the University of Brescia reviewed records for 315 non-diabetic patients with cognitive deficits, including 200 with biologically confirmed Alzheimer’s disease. All subjects underwent an assessment of insulin resistance using the TyG index and a clinical follow-up of 3 years. The results showed that when patients were divided according to their TyG index levels, those in the highest third of the Mild Cognitive Impairment subgroup deteriorated far more quickly than their lower-TyG peers.

The researchers found that high TyG was associated with blood-brain barrier disruption and cardiovascular risk factors, yet it showed no interaction with the APOE ε4 genotype. This suggests that metabolic and genetic risks may act through distinct pathways.

Identifying high-TyG patients could refine enrolment for anti-amyloid or anti-tau trials and prompt earlier lifestyle or pharmacological measures to improve insulin sensitivity.

“If targeting metabolism can delay progression, we will have a readily modifiable target that works alongside emerging disease-modifying drugs,” concluded Dr. Bianca Gumina.

The study aimed to fill the gap in understanding how quickly Alzheimer’s progresses by focusing on its impact during the prodromal mild cognitive impairment (MCI) stage.

This research has significant implications for individuals with mild cognitive impairment and their families, as it could provide a simple and cost-effective way to predict the pace of cognitive decline.

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