Combining cerebrospinal fluid and PI-2620 tau-PET for biomarker-based stratification of Alzheimer's disease and 4R-tauopathies.

Introduction: Recent advances in biomarker research have improved the diagnosis and monitoring of Alzheimer's disease (AD), but in vivo biomarker-based workflows to assess 4R-tauopathy (4RT) patients are currently missing. We suggest a novel biomarker-based algorithm to characterize AD and 4RTs.
Methods: We cross-sectionally assessed combinations of cerebrospinal fluid measures (CSF p-tau ₁₈₁ and t-tau) and ¹⁸ F-PI-2620 tau-positron emission tomography (PET) in patients with AD (n = 64), clinically suspected 4RTs (progressive supranuclear palsy or corticobasal syndrome, n = 82) and healthy controls (n = 19).
Results: Elevated CSF p-tau ₁₈₁ and cortical ¹⁸ F-PI-2620 binding was characteristic for AD while normal CSF p-tau ₁₈₁ with elevated subcortical ¹⁸ F-PI-2620 binding was characteristic for 4RTs. ¹⁸ F-PI-2620-assessed posterior cortical hypoperfusion could be used as an additional neuronal injury biomarker in AD.
Discussion: The specific combination of CSF markers and ¹⁸ F-PI-2620 tau-PET in disease-specific regions facilitates the biomarker-guided stratification of AD and 4RTs. This has implications for biomarker-aided diagnostic workflows and the advancement in clinical trials.
Highlights: Novel biomarker-based algorithm for differentiating AD and 4R-tauopathies. A combination of CSF p-tau ₁₈₁ and ¹⁸ F-PI-2620 discriminates AD versus 4R tauopathies. Hypoperfusion serves as an additional neuronal injury biomarker in AD.
(© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)