In Alzheimer’s disease, a protein (peptide) forms clumps in the brain and causes people to lose their memory. In a recent article, a research group at Uppsala University described a new treatment that increases the body’s breakdown of the building blocks that make these protein clumps.
In Alzheimer’s disease, the amyloid beta peptide begins to form clumps in the brain. This process is called aggregation, and the clumps that are created in this way are called aggregates. The treatments for Alzheimer’s disease currently in clinical trials are attempts to bind to these disease-causing aggregates. But they are unable to bind to the smallest aggregates that many now believe are the most toxic to neurons.
The treatment method developed in the new Uppsala research study with mice breaks down the building blocks from which these aggregates form before they can aggregate. This method of treatment therefore reduces the formation of all types of aggregates.
It has long been known that the peptide somatostatin, used by researchers in the Uppsala group, can activate the body’s own breakdown of amyloid beta, the peptide that makes the aggregates. In the past, however, it was not possible to use somatostatin as a drug because it has a very short half-life in the blood of just a few minutes and does not cross the blood-brain barrier into the brain where the aggregates are formed.
“To use somatostatin as a treatment, we fused it with a brain transport protein that allows somatostatin to enter the brain. This has been found to be very effective. When we used the transport protein, we also saw that the time the somatostatin stayed in the brain increased to several days, which is fantastic, ”says Fadi Rofo, PhD student in the Department of Pharmaceutical Biosciences and lead author of the study.
In the study, the researchers saw the greatest effects in the hippocampus, the part of the brain that makes memories, and the first part that is affected by Alzheimer’s disease.
“The fact that we have seen that the effect is most pronounced in the hippocampus in particular is very good. We hope that this method can be very targeted and has few side effects, which were a problem in other studies, ”says Greta Hultqvist, researcher at the Department of Pharmaceutical Biosciences who led the research study.
The study was done in mice, but the researchers believe that somatostatin would have the same effects in humans and that this type of treatment could be more effective than those previously tested.
Alzheimer’s disease is caused by the buildup of the peptide amyloid beta in the brain. This clumping is called aggregation. Amyloid-beta, not in an aggregated form, is present in all humans and does not cause disease. However, when it starts to aggregate, it becomes toxic. These aggregates are initially so small that they cannot be seen with a microscope. When they are that small, they can move freely around the brain and damage neurons. When enough neurons die, you have a hard time remembering things.
The aggregates continue to grow and eventually become so large that you can see them with the naked eye. This is called plaque. Plaque is present in much of the brain in people who have died of Alzheimer’s.
It used to be believed that these plaques were the bad guy, but now most researchers believe that they don’t do a lot of damage because they are large and immobile. Rather, the tiny aggregates are the most dangerous. Even these aggregates vary widely in size, and the smallest ones have been very difficult to target with various treatments.