235 Summary & Discussion The future of tau PET Tau PET in the clinic Tau PET is gradually moving toward clinical application as a diagnostic and possibly prognostic marker and as a selection- and monitoring tool in clinical trials. Assessing the value of tau PET in routine clinical workup is an essential step towards implementation of tau PET in the clinic. So far, two studies demonstrated added clinical value for tau PET in the clinic, by showing a statistically significant change in diagnosis and medication [22] and increased diagnostic certainty with including tau PET in the diagnostic workup [22, 23]. These studies represent a start in the assessment of the role of tau PET in routine clinical workup, but further exploration in different cohorts is key for implementation on larger scale. In the Netherlands, recently the TAP-TAU project was initiated. This prospective, longitudinal, multicenter study aims to mimic “real-world” clinical practice by including n=300 individuals in prodromal/mild dementia stages who might benefit most from tau PET ([18F]flortaucipir). Identifying which individuals might benefit most from tau PET is of major importance for its implementation and concepts for ‘Appropriate Use Criteria’ are currently being composed. In the TAP-TAU project individuals are thought to benefit most from addition of tau PET to the clinical workup is there is suspicion of mixed pathology, an atypical presentation, and/or conflicting biomarker results during routine diagnostic work-up. Tau PET in clinical trials A relevant open question in the current AD biomarker landscape lies in the comparison of tau PET and blood based biomarkers. The development of blood based biomarkers has progressed at a tremendous pace and requires critical rethinking of the role of tau PET in the current landscape. Blood based biomarkers for tau have – like tau PET - shown to correlate with post-mortem AD pathology, differentiate AD from other types of dementia, and predict future disease progression [1]. In addition, they have the advantage of cost-effectiveness and accessibility, which may lead to a transformation in the AD disease field (including clinical trials). However, tau PET still has some important advantages over blood based biomarkers for tau. One of these advantages is specificity, since some studies show that plasma p-tau217 for example does not only associate with tau pathology, but also with amyloid pathology [24], hampering the interpretability and implementation of plasma p-tau217 levels in clinical trials. In addition, biofluid and neuroimaging markers of tau pathology seem to convey partly independent information, with fluid markers being more tightly linked with early markers of AD (especially Aβ-pathology), while tau PET shows the strongest associations with cognitive and neurodegenerative 9
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