Biomarkers.

Background: Tau-PET is a diagnostic tool with high sensitivity and high specificity for discriminating Alzheimer Disease (AD) dementia from other neurodegenerative disorders in well-controlled research environments. The role of tau-PET in "real-world" clinical practice, however, remains to be established. We hypothesize that tau-PET will lead to some changes of the pre-PET clinical diagnosis and will improve diagnostic certainty and patient management in patients with considerable diagnostic uncertainty. The aim of the TAP-TAU study is therefore to investigate the impact of tau-PET in clinical practice.

Method: The TAP-TAU study, is a prospective, longitudinal multi-center study in 300 patients (≥50 years old) with prodromal or mild dementia recruited in six Dutch memory clinics. Patients are eligible if diagnostic certainty is <85% after routine dementia screening and if the differential diagnosis includes AD. For example, patients i) are suspected of having mixed pathology (e.g., AD and vascular pathology), and/or ii) have an atypical clinical presentation, and/or iii) show conflicting or inconclusive outcomes on other biomarkers (e.g., magnetic resonance imaging or cerebrospinal fluid). Participants will undergo a [F]flortaucipir tau-PET scan, blood-based biomarker sampling, and fill out patient wellbeing surveys (Figure 1). The primary outcome measures are change (pre- versus post- tau-PET) in diagnosis, diagnostic certainty, patient management and patient wellbeing. Secondary outcome measures are head-to-head comparisons between tau-PET and less-invasive, lower cost and more scalable diagnostic tools such as novel blood-based biomarkers and artificial intelligence based classifiers. A control group will be formed by patients who do not wish to undergo any study intervention (n=60). All participants will be followed for a year in the memory clinic.

Result: The first participants will be enrolled in March 2024.

Conclusion: In TAP-TAU, we will investigate the added clinical value of tau-PET in a real-world clinical setting, including memory clinic patients with limited diagnostic certainty after routine work-up. Findings of our study may contribute to recommendations regarding which patients may benefit most from assessment with tau-PET. This study is timely in the dawning era of disease-modifying treatments as vigilance concerning mixed pathologies and atypical presentations in the memory clinic population grows.