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.