12 Chapter 1 Figure 2. Neurofibrillary tangle (tau pathology) and plaque (amyloid pathology) development in AD (adapted from Van der Kant et al. Nature Reviews (2020) [9]). Whereas an AD diagnosis used to be based on clinical symptomatology, nowadays there is a shift towards a neurobiological diagnosis of the disease. The AT(N) classification provides a framework to diagnose AD based on biomarkers providing an indication of these pathologic changes [11]. In this framework, individuals are not only classified by the presence or absence of amyloid (plaques, ‘A’) and hyperphosphorylated tau (neurofibrillary tangles, ‘T’), but also by neurodegeneration or neuronal injury (‘N’). Biomarker status can be determined using positron emission tomography (PET). PET is a molecular imaging technique that allows the visualization of many physiological processes in vivo. Visualizing AD pathology in vivo became possible in 2004 with the introduction of the amyloid-specific PET tracer [11C]Pittsburgh Compound-B, also known as [11C]PIB [12-14]. Since then, amyloid PET has been researched extensively, multiple amyloid PET tracers have been developed and nowadays several of these amyloid PET tracers are approved for clinical use. Although amyloid PET can be used to determine ‘A’ status in the AT(N) classification system, experience with amyloid PET has shown that, apart from its limited regional specificity and between-person variability, amyloid PET does not (or maximally very minimally) associate with cognitive performance in AD. In contrast, tau pathology does show regional specificity and large between-person variability, but more importantly, tau pathology associates with cognitive performance in AD. This makes imaging of tau pathology in vivo of great interest. PET imaging of tau pathology became possible only several years ago, and since the first PET tracers for (AD-specific) tau pathology became available (first-generation tau PET tracers), nowadays multiple tau PET tracers (both first and second generation) are available for research purposes [15]. These tracers bind specifically to the AD-specific tau
RkJQdWJsaXNoZXIy MjY0ODMw