Exosomes Shown to Be Involved in Spread of Amyloid Beta in Alzheimer’s

Researchers at Linköping University study how Alzheimer’s disease spreads in the brain. [Thor Balkhed/Linköping University]

Researchers report that exosomes appear to play a key role in the spread of Alzheimer's disease in the brain. Long understood that the main task of exosomes was to help the cell get rid of waste products, it’s now known that exosomes can contain both proteins and genetic material, which other cells can absorb, explain the scientists.

In a new study (“Alzheimer’s Disease Pathology Propagation by Exosomes Containing Toxic Amyloid-Beta Oligomers”), published in Acta Neuropathologica, a team at Linköping University says that exosomes can transport toxic aggregates of amyloid beta (Aβ), thus spreading the disease to new neurons. Aggregated Aβ is one of the main findings in the brains of patients with Alzheimer's disease, the other being aggregates of the tau protein. As time passes, they form ever-increasing deposits in the brain, which coincides with the death of nerve cells. 

“The gradual deterioration of cognitive functions in Alzheimer’s disease is paralleled by a hierarchical progression of amyloid-beta and tau brain pathology. Recent findings indicate that toxic oligomers of amyloid-beta may cause propagation of pathology in a prion-like manner, although the underlying mechanisms are incompletely understood. Here we show that small extracellular vesicles, exosomes, from Alzheimer patients’ brains contain increased levels of amyloid-beta oligomers and can act as vehicles for the neuron-to-neuron transfer of such toxic species in recipient neurons in culture. Moreover, blocking the formation, secretion or uptake of exosomes was found to reduce both the spread of oligomers and the related toxicity. Taken together, our results imply that exosomes are centrally involved in Alzheimer’s disease and that they could serve as targets for development of new diagnostic and therapeutic principles,” write the investigators.

“The spread of the disease follows the way in which parts of the brain are anatomically connected. It seems reasonable to assume that the disease is spread through the connections in the brain, and there has long been speculation about how this spread takes place at the cellular level,” says Martin Hallbeck, M.D., Ph.D., associate professor in the department of clinical and experimental medicine at Linköping University and senior consultant of clinical pathology at Linköping University Hospital.

In a collaboration with researchers at Uppsala University, he and his co-workers have investigated exosomes in brain tissue from deceased persons. The research team at Linköping University found more Aβ in exosomes from brains affected by Alzheimer's disease than in healthy controls. Furthermore, the researchers purified exosomes from the brains from people with Alzheimer's disease, and investigated whether they could be absorbed by cells cultured in the laboratory.

“Interestingly, exosomes from patients were absorbed by cultured neurons, and subsequently passed on to new cells. The cells that absorbed exosomes that contained Aβ became diseased,” explains Dr. Hallbeck.

The scientists treated the cultured neurons with various substances that prevent exosomes from being formed, released, or absorbed by other cells. They were able to reduce the spread of the aggregated Aβ between cells by disrupting the mechanism in these ways. 

“Our study demonstrates that it is possible to influence this pathway, and possibly develop drugs that could prevent the spreading. The findings also open up the possibility of diagnosing Alzheimer's disease in new ways, by measuring the exosomes,” notes Dr. Hallbeck.