Boosting glycogen breakdown in neurons with tau-related damage improves symptoms of neurodegeneration, a potential strategy for Alzheimer's and related diseases. Digest
Neurodegenerative diseases like Alzheimer's disease and frontotemporal lobar degeneration are characterized by the abnormal buildup of tau, a protein that damages brain cells and drives cognitive decline. A recent study found that tau-related disorders in both fruit flies and humans are closely linked to neuronal accumulation of glycogen—the stored form of glucose—and that breaking down this glycogen substantially reduces tau-related brain damage.
In this study, researchers used fruit flies genetically engineered to produce a harmful form of human tau protein, as well as neurons derived from human stem cells taken from people with frontotemporal lobar degeneration. They tested how diet and enzymes involved in glycogen breakdown affected brain cell health, analyzed molecular changes through metabolomics and genomics, and examined how tau protein interacts with glycogen inside cells.
You just missed this in your inbox
Every other week our Premium Members received this exact study plus Rhonda's practical commentary and 8+ other hand-picked papers.
They found that both fruit flies and human neurons with tau-related damage had unusually high levels of glycogen. When they boosted the activity of an enzyme called glycogen phosphorylase, which breaks down glycogen, symptoms of tauopathy improved dramatically: The fruit flies showed fewer signs of neurodegeneration, and human neurons became healthier. Dietary restriction had similar effects by naturally increasing glycogen breakdown, redirecting glucose metabolism away from energy production and toward a stress-reducing pathway called the pentose phosphate pathway.
These findings suggest that tau-related brain diseases worsen when glycogen builds up in neurons, and that breaking down this excess sugar protects brain cells. By interrupting what appears to be a vicious cycle between glycogen and tau accumulation, this approach could offer a powerful new direction for treating Alzheimer's disease, frontotemporal lobar degeneration, and related conditions. Intermittent fasting promotes the breakdown of glycogen, likely contributing to its brain-protective effects. Learn more in this clip featuring Dr. Mark Mattson.