They are tiny particles, with potentially enormous human consequences. Researchers at Aarhus University have discovered a defect in the way 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 insights 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 that 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 quality of exosomes in cells that we know are predisposed to Alzheimer’s.”
SORLA mutation weakens exosome production
Scientists have identified four primary genes linked to inherited forms of Alzheimer’s. One of them is Sorl1, which contains the instructions for making the SORLA protein. When the SORLA protein carries a mutation, it increases a person’s risk of developing Alzheimer’s. According to Kristian Juul-Madsen and his colleagues, defects in this protein impair 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 cells where the SORLA protein is not mutated.”
Why the quality of exosomes is important for the brain
This discovery could be an important step forward for Alzheimer’s research, he explains.
“This tells us that exosomes produced particularly by immune cells in the brain play an important role in maintaining brain health, and that mutations that lead to fewer and poorer quality exosomes are associated with an increased risk of Alzheimer’s.”
Kristian Juul-Madsen believes that this knowledge could eventually contribute to advances in the treatment of Alzheimer’s.
“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 cells produce more and better exosomes, or by targeting other known receptors that can improve exosome production.”
A growing need for new therapies for Alzheimer’s
Alzheimer’s is the most common form of age-related dementia in Denmark. An estimated 55,000 Danes are living with the disease and effective treatment options are still lacking.
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