Research from the Buck Institute reveals that glycogen accumulation in neurons exacerbates tauopathy diseases such as Alzheimer’s by impairing oxidative stress management. Restoration of glycogen phosphorylase activity reduces tau pathology and promotes rerouting of sugar metabolism through the pentose phosphate pathway, enhancing neuroprotection. These findings illuminate mechanisms possibly underlying GLP-1 drug benefits observed in dementia and open avenues for novel therapeutic strategies targeting brain glycogen metabolism.