Alzheimer’s researchers are exploring a novel approach to combat dementia: targeting the brain’s stored glucose, or glycogen. A new study published in *Nature Metabolism* reveals that breaking down glycogen in the brain may reduce the formation of toxic proteins linked to Alzheimer’s disease. The research suggests that glycogen breakdown plays a critical role in maintaining brain health and could be a promising target for developing treatments.
Dr. Pankaj Kapahi, a professor at the Buck Institute for Research on Aging, led the study, which initially tested effects on fruit flies genetically modified to mimic tauopathy—a condition where the protein tau accumulates in the brain, similar to what occurs in Alzheimer’s. The flies exhibited brain damage and shortened lifespans. To assess potential human relevance, researchers also used lab-grown nerve cells from Alzheimer’s patients and postmortem brain samples from affected individuals.
The findings indicated that excessive glycogen and impaired breakdown were present in both fly and human models. Previously, research assumed glycogen was primarily stored in muscles and the liver, not the brain. However, the study revealed that excess glycogen contributed to disease by interacting with tau proteins, blocking their breakdown and leading to cell damage. Researchers discovered that stimulating the enzyme glycogen phosphorylase (GlyP) could reduce damage in fly and human nerves, suggesting that enzymes responsible for breaking down brain sugar might offer new therapeutic targets.
The team also investigated whether dietary interventions could improve brain health. Reducing protein intake in the flies resulted in extended lifespans and improved brain health, which correlated with increased glycogen breakdown. This led to the study’s key finding: glycogen breakdown in neurons may protect the brain from damage caused by tau buildup. A drug derived from a special molecule, 8-Br-cAMP, was developed to replicate the effects of dietary restriction, though the researchers caution against recommending low-protein diets immediately.
Dr. Michael Okun, a Florida neurologist and medical advisor to the Parkinson’s Foundation, praised the study’s potential implications but emphasized that the findings need further validation. He noted that broken-down glycogen may be used in antioxidant pathways to neutralize harmful free radicals in the brain. However, the study has limitations, as it was conducted on fly and human cell models without human trials. Scientists remain cautious about whether targeting glycogen breakdown could prevent human brain cell death and the safety of such interventions.
Alzheimer’s disease, the most common form of dementia in the U.S., affects over seven million people, according to the Alzheimer’s Association. Despite no known cure, current treatments only temporarily slow the disease’s progression. This study highlights an emerging avenue for research and offers hope for future strategies, including dietary or pharmacological approaches, to address the devastating impact of Alzheimer’s and related neurological conditions.