In Sweden, around 100,000 people are currently living with Alzheimer's disease. The number of people with Alzheimer's disease will increase as a consequence of increased life expectancy. The aim of the project is to develop positron emission tomography (PET, medical imaging technique) of soluble forms of the protein amyloid-beta (Abeta). The current PET technique, which is based on imaging the characteristic senile plaques consisting of insoluble accumulations of Abeta, is not satisfactory because the signal "hits the ceiling" early in the disease. A PET scan therefore provides no information about the severity of the disease and cannot be used to measure drug effects. The antibody we have previously developed, mAb158, binds selectively to Abeta protofibrils, but like all other antibodies, it is a large molecule that has difficulty crossing from the blood into the brain. Over the past year, we have modified mAb158 so that, in addition to protofibrils, it also binds to the transferrin receptor, increasing the transport of mAb158 into the brain. Depending on the modification, we have increased the uptake of the antibody 10-50 times. Furthermore, we have shown with PET that it is possible to image protofibrils in the brain in models of Alzheimer's disease. We will now study how sensitive the ligand is to changes in protofibril levels and further develop it for use in humans. The project is the first ever to successfully use an antibody as a PET ligand for a target system in the brain.