Mannose Promotes β-Amyloid Pathology by Regulating BACE1 Glycosylation in Alzheimer's Disease.

ABSTRACT: Hyperglycemia accelerates Alzheimer's disease (AD) progression, yet the role of monosaccharides remains unclear. Here, it is demonstrated that mannose, a hexose, closely correlates with the pathological characteristics of AD, as confirmed by measuring mannose levels in the brains and serum of AD mice, as well as in the serum of AD patients. AD mice are given mannose by intra-cerebroventricular injection (ICV) or in drinking water to investigate the effects of mannose on cognition and AD pathological progression. Chronic mannose overload increases β-amyloid (Aβ) burdens and exacerbates cognitive impairments, which are reversed by a mannose-free diet or mannose transporter antagonists. Mechanistically, single-cell RNA sequencing and metabolomics suggested that mannose-mediated N-glycosylatio

SUBMITTER: Liang C 

PROVIDER: S-EPMC11884605 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature