Glucosamine, a popular joint supplement, linked to faster Alzheimer’s progression

 

A widely used supplement for joint pain has been linked to a potentially concerning outcome in people with early cognitive problems.

Researchers at the University of Florida found that glucosamine use was associated with a greater likelihood that mild cognitive impairment would progress to dementia. Mild cognitive impairment, often shortened to MCI, describes measurable problems with memory or thinking that are greater than expected with normal aging but do not necessarily interfere substantially with everyday life.

The findings come from a large retrospective analysis of patient health records, supported by experiments involving human brain tissue and mouse models of Alzheimer's disease. The results remain preliminary and will need to be tested in a human clinical trial, but the researchers say they add to growing evidence that disrupted metabolism may play an important role in neurodegeneration.

The study was published in Nature Metabolism.

A Popular Supplement Comes Under Scrutiny

"In the United States, there are about 7 million people living with Alzheimer's and millions more with related dementias such as Lewy body or frontotemporal dementia," said senior author Ramon Sun, Ph.D., director of the Center for Advanced Spatial Biomolecule Research and associate director for innovation of UF's McKnight Brain Institute. "A lot of these people actively take an over-the-counter supplement that could be making their disease progression worse."

Glucosamine is widely sold without a prescription and is especially popular among older adults who take it for joint discomfort and joint health. Because of how commonly it is used, the researchers wanted to know whether it might influence Alzheimer's disease and related dementias, known as ADRD.

Working with Yi Guo, Ph.D., and Jiang Bian, Ph.D., the team used artificial intelligence to analyze deidentified UF Health records collected from 2012 to 2024.

The researchers focused on patients diagnosed with either ADRD or mild cognitive impairment, or MCI. In both groups, 8% of patients reported using glucosamine. That included 1,896 people with ADRD and 2,750 people with MCI.

Glucosamine Linked to Dementia Progression

After accounting for age, sex and demographics, the researchers found that glucosamine use was associated with a 25% higher likelihood that mild cognitive impairment would progress to dementia.

Among people who already had ADRD, glucosamine use was also associated with a 25% higher mortality risk, meaning a greater likelihood of death during a defined period of time.

The researchers did not observe that mortality association in the MCI group. That difference suggests glucosamine may have a stronger effect once dementia is already established.

Importantly, the health record findings do not show that glucosamine itself causes dementia to progress. Observational studies can reveal associations, but other differences between people who take a supplement and those who do not may contribute to the results.

"The electronic health record data are very provocative," said Matt Gentry, Ph.D., chair of UF's Department of Biochemistry and Molecular Biology and a study co-author. "While it's an association and not proof of causality, it does raise an important clinical question that now deserves much more attention."

A Metabolic Pathway May Help Explain the Link

The researchers also uncovered evidence of a biological mechanism that could help explain the association.

Their work points to a metabolic pathway involving the attachment of sugar structures to proteins. This process is a normal and important part of cell biology, but the researchers found signs that it becomes excessively active in Alzheimer's disease.

Sun said that abnormal activity in this pathway could eventually become a target for new treatments.

"Our results suggest that altered metabolism is a significant contributor to Alzheimer's progression and, in addition, addressing the metabolic defect could be an important complement to approaches focused on Alzheimer's plaques and tangles," Sun said.

Plaques and tangles are two of the best known features of Alzheimer's disease. Plaques are abnormal deposits of a protein called amyloid beta that accumulate between brain cells, while tangles are twisted forms of the tau protein that develop inside neurons. Much Alzheimer's research has traditionally focused on these abnormalities, but scientists are increasingly studying additional processes that may contribute to the disease.

Mapping Thousands of Molecules in the Brain

A spatial technology developed in Sun's laboratory helped researchers examine the metabolic changes in much greater detail.

"This technology allows us to examine thousands and thousands of molecules created when the body breaks down food or drugs and to uncover intricate pathways that otherwise would stay hidden," Sun said.

The team then focused specifically on glucosamine. Glucosamine is a naturally occurring, sugar-related molecule that can cross the blood-brain barrier, the protective boundary that tightly controls which substances can move from the bloodstream into brain tissue.

Once inside the brain, glucosamine can enter biochemical pathways that construct complex sugar structures and attach them to proteins. Commercial glucosamine supplements can be produced from materials including shellfish shells or corn.

According to the researchers, the effects of glucosamine may depend heavily on the biological environment in which it is acting. A healthy brain and a brain affected by Alzheimer's may therefore respond differently to the same molecule.

The Alzheimer's brain appeared to be particularly vulnerable to this metabolic pathway.

Mouse Experiments Point to a Possible Mechanism

To explore the mechanism more closely, the scientists studied genetically modified mice.

Glucosamine significantly increased the attachment of sugar residues to proteins inside cells. At the same time, glucosamine-treated mice developed worse deficits in "social memory" -- or memory of recognition -- compared with the other animals.

When the researchers used a chemical treatment to suppress the sugar attachment process, memory performance improved.

That experiment suggested that excessive sugar tagging could play a direct role in the memory problems seen in the animals rather than simply occurring alongside them.

Human Alzheimer's Brain Tissue Shows the Same Pattern

The researchers next examined human brain tissue with Stefan Prokop, M.D.

Brain specimens from people with Alzheimer's disease, provided by the UF Neuromedicine Brain and Tissue Bank, showed significantly more sugar attachment than tissue from normal controls.

Combined with the mouse experiments and health record analysis, the findings suggest that abnormal metabolism may be more than a secondary consequence of Alzheimer's disease. The researchers reported that it could instead contribute to the disease process itself.

"Proteins are the cell's 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," Gentry said. "What we found in Alzheimer's is that this sugar-tagging system appears to be overactive. The Alzheimer's brain is adding too many of these sugar structures, and this seems to contribute to the disease rather than protect against it."

The results raise a potentially important question about glucosamine use among people with cognitive impairment or dementia, but they do not yet establish that people should stop taking the supplement. A controlled human clinical trial will be needed to determine whether glucosamine directly accelerates Alzheimer's progression and, if so, which patients may be most vulnerable.

Journal Reference:

1. Tara R. Hawkinson, Zizhen Liu, Roberto A. Ribas, Terrymar Medina, Rikke S. Nielsen, Harrison A. Clarke, Xin Ma, Angela C. Mueller, Adrielle F. Plasencia, Alexander L. Sheer, Samantha T. Simpson, Charles M. Soto, Jessica Sudderth, Feng Cai, Alex R. Cantrell, Matthieu G. Colpaert, Cameron J. Shedlock, Lei Wu, Lyndsay E. A. Young, Damon D. Kooser, Li Chen, Alison M. Ryan, Sadi Quinones, Jihye Son, Parastoo Azadi, Ralph J. Deberardinis, Stefan Prokop, Derek Allison, Shuang Yang, Hongyu Chen, Yu Huang, Xing He, Kimberly M. Alonge, Jingchuan Guo, Yi Guo, Jiang Bian, Craig W. Vander Kooi, Matthew S. Gentry, Ramon C. Sun. Hyperglycosylation is a metabolic driver of Alzheimer’s disease. Nature Metabolism, 2026; 8 (6): 1410 DOI: 10.1038/s42255-026-01538-4

Courtesy:

UF Health. "Glucosamine, a popular joint supplement, linked to faster Alzheimer’s progression." ScienceDaily. ScienceDaily, 27 September 2026. <www.sciencedaily.com/releases/2026/09/260927033754.htm>.

 

 

 

 

A massive genetic study of cat tumors reveals striking similarities to human cancer and could open new paths to treatment for both species

 

Scientists have taken a major step toward understanding cancer in cats, opening what researchers once described as a genetic "black box."

In a large international study published in Science, researchers genetically analyzed cat cancers on a scale that had not been attempted before. The work could improve cancer care for cats while also helping scientists better understand how some cancers develop in humans and other animals.

The researchers also created a freely available resource that other scientists can use to study the genetics of feline cancer.

Cancer is one of the leading causes of illness and death in cats, yet scientists have historically known far less about the genetic changes behind feline tumors than they do about cancers in humans or dogs.

Dr. Geoffrey Wood, a University of Guelph pathobiology professor and co-senior author of the study, said that gap has now begun to close.

"Despite domestic cats being common pets, there was very little known about the genetics of cancer in these animals," Wood says, "until now."

Cat and Human Cancers Share Key Genetic Changes

Researchers examined tumor samples from almost 500 domestic cats in five countries, searching for mutations and other genetic changes that help cancers form and grow.

Many cancers are driven by changes in certain genes that normally help control how cells grow, divide, repair damage, or die. When these genes are altered, cells can begin multiplying uncontrollably. Scientists often refer to genes that contribute directly to tumor growth as cancer driver genes.

The team found that many of the driver genes involved in cat cancers were also familiar from human and dog cancers.

One of the clearest examples appeared in aggressive mammary cancers, which arise in breast tissue.

The most common driver gene found in cat mammary tumors was FBXW7. More than 50 percent of the tumors examined carried a mutation in this gene.

FBXW7 normally helps regulate proteins involved in cell growth and division. When the gene is damaged, some of those growth promoting proteins can accumulate, potentially helping cancer cells survive and spread.

In humans, mutations in the FBXW7 gene in breast cancer are associated with worse prognosis - paralleling the change seen in cats.

Researchers also identified similarities between cat and human cancers affecting the blood, bones, lungs, skin, gastrointestinal system and central nervous system.

Shared Environments May Offer Cancer Clues

The similarities may be especially useful because domestic cats often live in the same environments as people.

Cats can encounter some of the same environmental factors as their owners, including household chemicals, air pollutants, smoke and other exposures that may influence cancer risk. Studying naturally occurring cancer in pets could therefore help researchers investigate how genetics and the surrounding environment interact.

"This study can help us understand more about why cancer develops in cats and humans, how the world around us influences cancer risk, and possibly find new ways to prevent and treat it," says Wood.

The genetic findings could also have implications for treatment.

Researchers found that certain chemotherapy drugs were more effective against cat mammary tumors carrying the mutated FBXW7 gene.

The result was observed only in tissue samples, so it does not yet show that the same approach will work in living cats or people. Still, the finding suggests that genetic information could eventually help doctors and veterinarians identify treatments that work better for particular tumors.

This type of approach is known as precision oncology. Instead of treating every cancer of the same general type in exactly the same way, precision oncology uses the molecular and genetic features of an individual tumor to help guide therapy.

"Having access to such a large set of donated tissues allowed us to assess drug responses across tumor types," says Dr. Sven Rottenberg, co-senior author at the University of Bern, "in a way that hasn't been possible at this scale before."

Bailey Francis, co-first author at the Wellcome Sanger Institute, said the findings could also have implications for dogs.

"When knowledge and data flows between different disciplines, we can all benefit."

Using Cat Cancer Research to Help Pets and People

The project brought together researchers from the Wellcome Sanger Institute, U of G's Ontario Veterinary College, the University of Bern and other institutions.

Rather than collecting all new samples, the team sequenced DNA from tissues that veterinarians had already obtained for diagnostic purposes.

That allowed scientists to study naturally occurring cancers from a large number of cats and compare the genetic patterns among different tumor types.

The findings also support a broader research strategy known as One Medicine.

The One Medicine approach emphasizes that human and veterinary medicine can inform one another. Cancer treatments developed for humans could potentially be evaluated in cats with naturally occurring tumors, while discoveries made during feline cancer studies and clinical trials could provide clues that help shape future human research.

That two way exchange is especially valuable because pets naturally develop many of the same diseases as people while sharing many aspects of the same environment.

Researchers hope the new genetic database will ultimately help bring more personalized cancer care to cats.

Dr. Louise Van Der Weyden, senior author at the Wellcome Sanger Institute, said the study provides a foundation for the next stage of feline cancer research.

"We can now begin to take the next steps forwards towards precision feline oncology, to catch up with the diagnostic and therapeutic options that are available for dogs with cancer, and ultimately one day, humans."

The research was funded in part by EveryCat Health Foundation, the CVS Group, Wellcome, the Natural Sciences and Engineering Research Council of Canada and the Swiss National Science Foundation.

Journal Reference:

1. Bailey A. Francis, Latasha Ludwig, Chang He, Melanie Dobromylskyj, Christof A. Bertram, Heike Aupperle-Lellbach, Hannah Wong, Aiden P. Foster, Mark J. Arends, Alejandro Suárez-Bonnet, Simon L. Priestnall, Laetitia Tatiersky, Fernanda Castillo-Alcala, Angie Rupp, Arlene Khachadoorian, Eda Parlak, Marine Inglebert, Shevaniee Umamaheswaran, Saamin Cheema, Martin Del Castillo Velasco-Herrera, Kim Wong, Ian C. Vermes, Jamie Billington, Sven Rottenberg, Geoffrey A. Wood, David J. Adams, Louise van der Weyden. The oncogenome of the domestic cat. Science, 2026; 391 (6787): 793 DOI: 10.1126/science.ady6651

Courtesy:

University of Guelph. "Scientists say house cats could help unlock better cancer treatments for humans." ScienceDaily. ScienceDaily, 26 September 2026. <www.sciencedaily.com / releases / 2026 / 09 / 260924231826.htm>.