PETABC – PET examinations of ABC transporter function for the diagnosis and stratification of dementia patients

ATP-binding cassette transporters (ABC transporters) such as ABCC1 and ABCA7 control the passage of endogenous and exogenous compounds from blood into brain and vice versa. The toxic metabolite amyloid-ß (Aß), which accumulates in Alzheimer's disease (AD), is transported from brain to blood by the ABCC1 transporter, and there is evidence that the ABCA7 transporter does actually play a role in neurodegenerative diseases (NDE) such as AD, Parkinson's disease and Lewy body dementia. The aim of the overall project is to develop imaging molecular probes that allow the transport capacities of ABCC1 and ABCA7 to be measured in individual patients with different NDE using positron emission tomography (PET), thereby enabling the stratification of patient populations for preventive measures.
The German project partner will design the ABCA7 probes and carry out extensive chemical derivatisation based on in silico defined lead structures. Following biological investigations into the specific properties of the new substances by project partners, the most suitable compounds are radioactively labelled and examined preclinically using PET with regard to their suitability for human use.