Fig. 6: Glucosamine increases brain N-glycans, worsens social memory in 5xFAD mice and is associated with adverse outcomes in real-world evidence of dementia cohorts.

a, A schematic of glucosamine entry into the hexosamine pathway, increasing N-acetyl-glucosamine and ER protein N-glycosylation. b, Experimental design: 8-month-old 5xFAD mice receive glucosamine or vehicle for 2 weeks followed by social memory testing. c,d, MALDI imaging and violin plots of representative two unique complex N-glycans (N-glycan structure shown on the left) showing higher brain N-glycan abundance in glucosamine-treated 5xFAD mice compared with water-treated controls. P values are indicated (two-tailed t-test). e, Social memory performance across four trials demonstrating impaired memory in glucosamine-treated 5xFAD mice (n = 6 animals) relative to vehicle-treated 5xFAD mice (n = 7 animals). Data are mean ± s.e.m. P values are indicated (two-way repeated-measures ANOVA for behaviour). f, A schematic of EHR cohort construction from non-dementia controls, MCI and dementia diagnoses (AD and ADRD) with identification of glucosamine exposure from medication records. g, The proportion of patients with documented glucosamine use in the MCI and ADRD cohorts. h, Ten-year all-cause survival curves for patients with ADRD with or without glucosamine use, showing reduced survival in glucosamine users. Data are mean ± 95% confidence intervals. i, Ten-year all-cause survival in patients with MCI, showing no significant difference between glucosamine users and non-users (log-rank P = 0.252). Data are mean ± 95% confidence intervals. j, The cumulative incidence of transition from MCI to AD over time, revealing a higher conversion rate among glucosamine users compared with matched non-users. Data are mean ± 95% confidence intervals. Panels created in BioRender: a, Sun, R. https://biorender.com/9uxxwcu (2026); b, Sun, R. https://biorender.com/ouipb70 (2026);f, Sun, R. https://biorender.com/1bixssx (2026).

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