![\"Spatial](\"https:\/\/cdn.sci.news\/images\/enlarge14\/image_15108e-Hyperglycosylation.jpg\")
<\/a><\/p>\nSpatial multiomics analysis reveals hyperglycosylation in human Alzheimer\u2019s brains. Image credit: Hawkinson et al., doi: 10.1038\/s42255-026-01538-4.<\/p>\n
\u201cIn the United States, there are about 7 million people living with Alzheimer\u2019s and millions more with related dementias such as Lewy body or frontotemporal dementia,\u201d said co-senior author Dr. Ramon Sun, director of the Center for Advanced Spatial Biomolecule Research and associate director for innovation of the University of Florida\u2019s McKnight Brain Institute.<\/p>\n
\u201cA lot of these people actively take an over-the-counter supplement that could be making their disease progression worse.\u201d<\/p>\n
As glucosamine is widely available and commonly used by seniors for joint health, Dr. Sun and colleagues set out to investigate whether it could have any effect in Alzheimer\u2019s disease and related dementias.<\/p>\n
They found that brains affected by Alzheimer\u2019s carry unusually high levels of N-glycans, sugar chains attached to proteins. They call this phenomenon \u2018hyperglycosylation.\u2019<\/p>\n
The increase appeared in brain tissue from deceased Alzheimer\u2019s patients and grew more pronounced in the brain\u2019s gray matter at later stages of the disease. It also appeared in two mouse models of the disease.<\/p>\n
\u201cProteins are the cell\u2019s molecular machines, and many of them need sugar tags added in just the right way to fold correctly, travel to the right place and do their jobs,\u201d said co-senior author Dr. Matt Gentry, chair of the University of Florida Department of Biochemistry and Molecular Biology.<\/p>\n
\u201cWhat we found in Alzheimer\u2019s is that this sugar-tagging system appears to be overactive.\u201d<\/p>\n
\u201cThe Alzheimer\u2019s brain is adding too many of these sugar structures, and this seems to contribute to the disease rather than protect against it.\u201d<\/p>\n
Experiments in mice suggested the cause is increased production of these sugar chains, not a failure to break them down.<\/p>\n
When the researchers reduced glycan production, either by silencing a gene called PGM3 or with a drug called NGI-1, mice with Alzheimer\u2019s-like disease did better on a social memory test.<\/p>\n
Giving the mice glucosamine, which feeds the glycan-building pathway, increased glycans in their brains and worsened their memory.<\/p>\n
Neither approach changed amyloid plaques, a hallmark of the disease.<\/p>\n
The scientists also reviewed electronic health records from the University of Florida\u2019s health system.<\/p>\n
Among patients with Alzheimer\u2019s-related dementias, those with documented glucosamine use for at least a year had about a 25% higher mortality risk.<\/p>\n
Among patients with mild cognitive impairment, glucosamine users were about 25% more likely to progress to dementia, though their survival did not differ significantly from non-users.<\/p>\n
About 8% of patients in the records were identified as glucosamine users.<\/p>\n
The authors caution that their human data are observational, and the findings do not prove that glucosamine causes harm in people. Glucosamine did not raise brain glycans or impair memory in healthy mice.<\/p>\n
\u201cOur results suggest that altered metabolism is a significant contributor to Alzheimer\u2019s progression and, in addition, addressing the metabolic defect could be an important complement to approaches focused on Alzheimer\u2019s plaques and tangles,\u201d Dr. Sun said.<\/p>\n