Researchers discover clues for Alzheimer’s disease in hibernation
Leuven, 12 November 2026 – Researchers at VIB and KU Leuven have discovered that hibernation triggers changes in brain cells that partially resemble those in Alzheimer’s disease. Studying golden hamsters, the team identified changes in gene expression across the hibernation cycle, which resemble those associated with the accumulation of amyloid plaques in Alzheimer’s. The findings, published in Science Advances, suggest that some early cellular changes associated with Alzheimer’s may also occur as part of a natural adaptive response, offering new ways to study the disease for therapy development.
Alzheimer’s disease affects millions of people worldwide and is characterized by the buildup of amyloid-β plaques and tangled tau proteins in the brain. These tangles contain abnormally phosphorylated tau—a form of the protein carrying excessive phosphate groups
Previous work has shown how natural processes such as hibernation and sleep induce reversible changes to tau, such as phosphorylation. In other words, hibernation offers a window into how the brain adapts to dramatic physiological changes. In this new study, the team sought to understand which biological processes are involved in hibernating brains, and what clues they might offer for Alzheimer’s disease.
“For the first time, we have mapped how gene activity changes across different brain cell types during the hibernation cycle. In hibernating hamsters, the connections between brain cells undergo structural changes alongside increased phosphorylation of tau, a protein also implicated in Alzheimer’s disease,” says Prof. Patrik Verstreken (VIB-KU Leuven Center for Neuroscience). “Studying these changes in a natural physiological process gives us a new way to investigate processes that also occur in dementia.”
Hibernation and reversible brain inflammation
To explore these changes, the researchers examined gene expression in the hippocampus – a brain area important for memory, among other things - of golden hamsters at different stages of hibernation and compared the findings with data from people with Alzheimer’s disease.
The analysis revealed an unexpected finding: some of the biggest changes occurred in the microglia, the brain’s immune cells. These cells activated inflammatory pathways similar to those seen in Alzheimer’s disease, suggesting that some responses we associate with disease may also form part of a normal physiological response that could help protect the brain.
“Because the Tau protein undergoes similar changes in both Alzheimer’s disease and hibernation, we wanted to find out whether the same processes might be at work in both. Surprisingly, although Tau is mainly found in neurons, the biggest changes during hibernation occurred in microglia, the brain’s immune cells. Even more strikingly, their response closely resembled the inflammatory response previously observed in the brains of people with Alzheimer’s disease,” adds Dr. Pablo Largo-Barrientos, co-first author of the study (VIB-KU Leuven for Neuroscience).
Building a stronger resource for hibernation and Alzheimer’s disease
More than these findings, the study provides a resource for other researchers to explore the cellular changes that accompany hibernation in the brain. By making this information available to the scientific community, they hope to help others investigate how the brain adapts to this process.
“One of the most immediate contributions of this study is the first single-cell atlas of a hibernating brain. It gives researchers a resource to explore how the genes and cell types they study change throughout hibernation,” says Largo-Barrientos.
The team now aims to move from mapping these changes to understanding their function and potential relevance to neurodegenerative disease.
“The next step is to identify which of these pathways and cellular changes are most important, reproduce them experimentally, and investigate how they relate to what happens in the diseased brain,” concludes Verstreken. “Ultimately, we hope that understanding how the brain adapts during hibernation will reveal mechanisms that could help us develop new approaches for people living with dementia.”
Publication
Common transcriptional changes in the brain during hibernation and Alzheimer’s disease. Largo-Barrientos, Praschberger, et al. Science Advances, 2026. DOI: 10.1126/sciadv.aeg3486
Funding
This research was supported by, VIB, KU Leuven, the European Research Council, the Chan-Zuckerberg initiative, the Rainwater Foundation, and Research Foundation Flanders - FWO.
João Cardoso
Kristof Windels
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