A recent study from the Buck Institute for Research on Aging has uncovered that brain sugar metabolism, specifically the breakdown of glycogen in neurons, may play a protective role against Alzheimer's disease and other forms of dementia.

In models of tauopathy, tau proteins bind to glycogen, which traps it and hinders its breakdown, thereby impairing the neuron’s capacity to manage oxidative stress—a critical factor in neurodegeneration.

The study found that increasing the activity of an enzyme known as glycogen phosphorylase (GlyP) can help clear excess sugar from neurons, leading to reduced tau accumulation and oxidative damage.

Moreover, dietary restriction (DR) has been shown to boost GlyP activity, yielding improved outcomes in tauopathy models, with pharmacological mimetics like 8-Br-cAMP able to replicate these beneficial effects.

The collaborative research approach, which integrated expertise from various fields such as fly aging, neurodegeneration, proteomics, and human induced pluripotent stem cells (iPSCs), significantly contributed to the study's findings.

The implications of the study suggest that GLP-1 drugs, while primarily used for weight loss, may also have therapeutic potential against dementia by mimicking the effects of dietary restriction and promoting healthy brain metabolism.

Researchers also observed similar glycogen accumulation and protective effects of GlyP in human neurons derived from patients with frontotemporal dementia, indicating a promising avenue for translational therapies.

Professor Pankaj Kapahi emphasized the significance of this research, noting that glycogen plays an active role in neurodegeneration rather than merely serving as an energy reserve.

The study's findings were bolstered by the collaborative efforts of various laboratories at the Buck Institute and Emory University, which contributed significantly to its methodologies and conclusions.

Interestingly, GlyP levels can be naturally increased through fasting, and this enzyme's activity may also be enhanced by GLP-1 receptor agonist drugs, which are typically prescribed for weight loss.