Hyperglycosylation fuels Alzheimer's progression, revealing a new therapeutic target

Nature Metabolism identifies hyperglycosylation as a driving metabolic factor in Alzheimer's disease, caused by increased glycan biosynthesis rather than reduced degradation. Across human AD brains and mouse models, elevated N-glycan production correlates with disease regions and severity; reducing glycosylation via PGM3 knockdown or OST inhibition improves cognitive outcomes in mice, while glucosamine supplementation raises brain glycans and worsens social memory. Real-world data also associate glucosamine use with accelerated progression and higher mortality in dementia cohorts. The findings propose glycan metabolism as an actionable therapeutic target and prompt clinical trials to assess glucosamine safety in dementia populations.