PET analyses of ABC transporter function for diagnostics and stratification of dementia patients

The export function of the blood-brain barrier (BBB) is moving continuously into the focus of research on neurodegenerative disorders (ND).

In 2011, we have described for the first time that the ABC transporter C1 (ABCC1) is exceptionally important for the export of metabolites from the brain, especially for amyloid-β(Aβ).

In 2019, the first ABCC1 mutation was found in a family with inherited clinical Frontotemporal Lobe Degeneration (FTD) and histological AD. ABCC1 belongs to the ABC transporter superfamily of which several members have been linked to NDs. Amongst them, a potential role of ABCA7 has been discovered in 2011 in a large NGS study.

We hypothesized that ABC transporter function can be used to determine the impairment and remaining capacity of the BBB export in individual patients in vivo with different NDs (AD, PD, LBD, PSP).

We now aim to translate our ABCC1 PET protocol to AD patients to assess whether cerebral ABCC1 function is impaired in comparison to age-matched healthy control subjects.

We also want to investigate the relevance of ABCC1 for the diagnostics of functional BBB-deficiency, which will allow better classification of patient groups. Another important part is the development of novel PET radiotracers for functional imaging for ABCA7.

Thus, we will perform in vitro and in vivo investigations by using cell culture BBB models, humanised mouse models, structural assessment, radiolabelling methods, and animal PET imaging.