Hyperglycosylation Maybe a Key Driver of Alzheimer’s Disease Progression

A new study identifies brain hyperglycosylation—an excessive buildup of sugar-containing glycans on proteins—as a pathological driver of Alzheimer’s disease (AD), revealing a promising new target for treatment. By integrating spatial metabolomics, lipidomics, glycomics, and advanced isotopic tracing techniques in transgenic AD mouse models and post-mortem human brain samples, researchers found that a conserved pattern of brain hyperglycosylation is caused by increased glycan biosynthesis. Experimental suppression of glycan-producing enzymes improved cognitive performance in AD mice, whereas oral glucosamine supplementation worsened cognitive outcomes. Supporting these findings, a retrospective analysis of electronic health records showed that glucosamine use among patients with AD was associated with faster disease progression and poorer survival, particularly in those with more severe disease. These results suggest that abnormal glycan metabolism plays a direct role in AD pathogenesis and that targeting hyperglycosylation may offer a novel therapeutic strategy for slowing disease progression. Source: https://www.nature.com/