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

Dilcher, Roxane; Wall, Stephan; Groß, Mattes; Katzdobler, Sabrina; Wagemann, Olivia; Palleis, Carla; Weidinger, Endy; Fietzek, Urban; Bernhardt, Alexander; Kurz, Carolin; Ferschmann, Christian; Scheifele, Maximilian; Zaganjori, Mirlind; Gnörich, Johannes; Bürger, Katharina; Janowitz, Daniel; Rauchmann, Boris‐Stephan; Stöcklein, Sophia; Bartenstein, Peter; Villemagne, Victor; Seibyl, John; Sabri, Osama; Barthel, Henryk; Perneczky, Robert; Schöberl, Florian; Zwergal, Andreas; Höglinger, Günter U.; Levin, Johannes; Franzmeier, Nicolai; Brendel, Matthias (2024): Combining cerebrospinal fluid and PI‐2620 tau‐PET for biomarker‐based stratification of Alzheimer's disease and 4R‐tauopathies. Alzheimer's & Dementia, 20 (10). pp. 6896-6909. ISSN 1552-5260

Abstract

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-tau181 and t-tau) and 18F-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-tau181 and cortical 18F-PI-2620 binding was characteristic for AD while normal CSF p-tau181 with elevated subcortical 18F-PI-2620 binding was characteristic for 4RTs. 18F-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 18F-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-tau181 and 18F-PI-2620 discriminates AD versus 4R tauopathies.
Hypoperfusion serves as an additional neuronal injury biomarker in AD.

• Doc-Type: Article (LMU Hospital)
• Organisational unit (Faculties): 07 Medicine > Munich Cluster for Systems Neurology (SyNergy); 07 Medicine > Medical Center of the University of Munich > Clinic and Polyclinic for Nuclear Medicine
• DFG subject classification of scientific disciplines: Life sciences
• DFG: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 491502892
• DFG: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 390857198