Scientists from the Karolinska Institute in Sweden, together with specialists from the RIKEN Brain Science Center in Japan, have identified two receptors in the brain — SST1 and SST4 — that can significantly influence the development of Alzheimer’s disease.

The study was published in the Journal of Alzheimer’s Disease.

These receptors regulate the activity of the enzyme neprilysin, which is responsible for breaking down beta-amyloid, a protein that forms toxic plaques when accumulated and is considered one of the main factors in neurodegeneration. The researchers studied the function of these receptors in mice with genetic modifications modeling Alzheimer’s disease, as well as in cell cultures.

When both receptors — SST1 and SST4 — were “turned off,” neprilysin activity dropped, and beta-amyloid rapidly accumulated in brain tissues. As a result, the animals exhibited memory decline and impaired cognitive-related behaviors.

The scientists then tested whether these receptors could be artificially activated. When a stimulating substance targeting SST1 and SST4 was administered to mice with an Alzheimer’s model, neprilysin levels significantly increased, and beta-amyloid concentrations decreased. This, in turn, improved memory and behavior. Importantly, this stimulation did not cause serious side effects, making the approach promising for future drug development.

The researchers note that SST1 and SST4 belong to the GPCR receptor class, which has long been considered convenient and accessible targets for drug therapy. Medications targeting such receptors can often be taken as regular oral tablets, which is an advantage over current antibodies used to treat Alzheimer’s disease, which are costly and carry a risk of side effects. The discovery of the role of these receptors could lay the foundation for a new generation of drugs aimed at activating the brain’s own protective mechanisms.