Scientists find a hidden weak spot that may trigger Alzheimer’s
Faulty exosomes caused by a SORLA mutation may unlock a powerful new target for Alzheimer’s treatment.
- Date:
- November 25, 2025
- Source:
- Aarhus University
- Summary:
- Scientists have found that a mutation tied to Alzheimer’s disrupts the production and quality of exosomes—tiny cell-made communication packets. Cells with the defective SORLA protein generate fewer exosomes and ones far less able to support nearby brain cells. This weakness may be a key driver of Alzheimer’s development. The research points to new treatment strategies that enhance or restore exosome function.
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They're tiny particles -- with potentially huge human consequences. Researchers at Aarhus University have uncovered a flaw in how cells form what are known as exosomes, and this defect is associated with a mutation found in some people living with dementia. The discovery may offer new insight into how Alzheimer's develops -- and potentially point toward future treatment strategies.
Exosomes are extraordinarily small. Millions of them could sit on the tip of a grain of rice. Despite their size, new findings from the Department of Biomedicine at Aarhus University suggest they may play a central role in Alzheimer's disease. Assistant Professor Kristian Juul-Madsen is part of the team behind the study, which recently appeared in Alzheimer's & Dementia: The Journal of the Alzheimer's Association.
"Exosomes are used to communicate with and activate surrounding cells, and we have now identified a defect in both the production and the quality of exosomes in cells that we know are predisposed to Alzheimer's."
SORLA Mutation Weakens Exosome Production
Scientists have identified four primary genes tied to inherited forms of Alzheimer's. One of these is Sorl1, which contains the instructions for making the protein SORLA. When the SORLA-protein carries a mutation, a person's risk of developing Alzheimer's increases. According to Kristian Juul-Madsen and his colleagues, defects in this protein disrupt the ability of brain cells to produce healthy exosomes.
"We found that cells with this mutation produced 30% fewer exosomes, and those that were produced were significantly worse at stimulating the growth and maturation of surrounding cells -- in fact, up to 50% less effective than in cells where the SORLA-protein is not mutated."
Why Exosome Quality Matters for the Brain
This discovery could be an important step forward for Alzheimer's research, he explains.
"It tells us that exosomes produced particularly by the brain's immune cells play an important role in maintaining brain health -- and that mutations leading to fewer and poorer quality exosomes are associated with increased risk of Alzheimer's."
Kristian Juul-Madsen believes these insights may eventually contribute to advances in Alzheimer's treatment.
"The potential is very clear. We now have the opportunity to investigate new treatments for Alzheimer's -- either by stimulating the function of SORLA so that the cells produce more and better exosomes, or by targeting other known receptors that can enhance exosome production."
A Growing Need for New Alzheimer's Therapies
Alzheimer's is the most common form of age-related dementia in Denmark. An estimated 55,000 Danes live with the disease, and effective treatment options are still lacking.
Story Source:
Materials provided by Aarhus University. Note: Content may be edited for style and length.
Journal Reference:
- Kristian Juul‐Madsen, Ina‐Maria Rudolph, Jemila P. Gomes, Katrina Meyer, Peter L. Ovesen, Malgorzata Gorniak‐Walas, Marianna Kokoli, Narasimha S. Telugu, Malthe von Tangen Sivertsen, Fabia Febbraro, Duncan S. Sutherland, Johan Palmfeldt, Sebastian Diecke, Olav M. Andersen, Matthias Selbach, Thomas E. Willnow. Familial Alzheimer\'s disease mutation identifies novel role of SORLA in release of neurotrophic exosomes. Alzheimer\'s, 2025; 21 (9) DOI: 10.1002/alz.70591
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