232 Chapter 9 in the choroid plexus, and its resulting spill-in in the hippocampus, hamper the correct measurement of tracer binding in this region. A large proportion of studies therefore disregard the hippocampus in their assessment. This topic needs to be addressed urgently, particularly since clinical trials are now moving to the earlier stages of AD, where the hippocampus becomes a crucial ROI. It could be that the method of ROI delineation plays a role. ROI delineation approached can be based on several principals. A recent study indicated that individualized ROIs carry an advantage over group-level ROIs for assessing longitudinal tau PET and can increase the sensitivity to detect treatment effects in AD trials [5]. Although several studies aimed to address the particular issue of the hippocampus [6, 7], future studies are warranted to find alternative approaches to solve this issue for [18F]flortaucipir. Ideally one would try to find a methodological solution that could be retrospectively applied to the thousands of already collected scans, independent of acquisition protocol. An approach to avoid this issue in the future is the development of other tau PET tracers that do not show off-target binding in the choroid plexus. Currently multiple tau PET tracers are available that do not show severe off-target binding in the choroid plexus. However, each of these tracers seem to have their own pitfalls, such as off-target binding in the meninges causing spill-in into cortical ROIs with [18F]MK-6240[8]. Larger studies focusing on head-to-head comparisons between tau PET tracers could aid in decision making regarding which tau PET tracer to use in different settings. It is important to realize that, irrespective of correct ROI delineation and tau PET tracer, parameters as obtained from the PET scan, like binding potential (BPND), represent proxies of tau pathology rather than a direct reflection of the amount of neurofibrillary tangles present in the brain. Although some studies assessed the comparison between tau PET tracer binding and histopathological neurofibrillary tangle burden within subjects [9], larger scale studies are required to gain better insight into the exact translation of PET derived parameters to histopathological changes. Tau PET as a predictive marker for progression Neuronal injury: structural MRI There is substantial (histopathological, in vitro and in vivo) evidence for the relationship between baseline tau pathology with neuronal injury (as reflected by decreased CBF as well as atrophy) in AD [10-17]. However, it was less well established whether (rate of) change in tau pathology also relates to (rate of) change in neuronal injury. Therefore, in chapter 7, we explored the longitudinal associations between tau pathology and markers of neuronal injury such as rCBF and atrophy. Our findings showed that higher tau load was related to accelerated cortical thinning, but
RkJQdWJsaXNoZXIy MjY0ODMw