11 General introduction Figure 2. Schematic overview of the SCIENCe project (8). A closer look at Alzheimer’s disease biomarkers Biomarkers of different modalities are used in the ATN classification. According to the framework, biomarkers for A include CSF amyloid-beta or amyloid burden on PET. Biomarkers for T include hyperphosphorylated (p-)tau in CSF or tau burden on PET. Biomarkers for N include atrophy on MRI, hypometabolism on fluorodeoxyglucose (FDG) PET, or total (t-)tau in CSF. In the following paragraphs, the different biomarkers and modalities will be discussed in more detail. Amyloid-targeting radioactive tracers such as [11C]PiB, [18F]florbetapir, [18F]flutemetamol and [18F]florbetaben allow for the simultaneous quantification of pathologic burden and visualization of its spatial distribution in the brain. For a large part of this thesis, [18F]florbetapir is used to quantify amyloid burden. In CSF, amyloid-beta 1-42 can be measured. Literature shows low values of CSF amyloid-beta and high amyloid burden 1