Abstract
Objectives Reliable biomarkers for detecting different abnormal tau protein isoforms between neurodegenerative diseases are currently missing. Phosphorylated tau (p-tau) in the cerebrospinal fluid (CSF) is acknowledged as a 3/4R tau biomarker in AD but not in other tauopathies. The positron emission tomography (PET) radiotracer 18F-PI-2620 has the potential to detect abnormal 3/4R-tau in patients with Alzheimer’s disease (AD) and 4R-tau in other tauopathies. This study investigates the interplay between tau-PET and CSF p-tau in AD and 4R-tauopathies.
Methods In this cross-sectional analysis, 52 patients with AD, 54 patients with PSP/CBS, and 11 controls underwent lumbar puncture and 0–60 min dynamic 18F-PI-2620 PET scanning. Independent t-tests assessed group differences in standardized uptake value ratios for the 20–40min time window (SUVr20–40) and p-Tau. Multiple regression analyses tested the association between SUVr20–40 and p-tau and group interactions. ROC analyses evaluated biomarker performance in differentiating patient groups. Quantitative and voxel-wise analyses were performed with R, SPM, and VoxelStats, controlling for age and sex.
Results Patients with AD showed elevated p-tau levels (p<0.05; >61 pg/ml) and SUVr20–40 in cortical regions, cingulate, insula, hippocampus, and amygdala (p<0.05). Patients with clinically suspected 4R-tauopathies showed low p-tau levels but demonstrated high SUVr20–40 in the globus pallidus (p<0.05), compared to controls and AD. ROC analyses showed high performance at discriminating patients with 4R-tau from those with AD in mainly temporal and parietal regions SUVr20–40(60–80%).
Conclusion The specific combination of CSF p-tau levels and 18F-PI-2620 PET SUVR in disease-specific regions facilitates biomarker-guided stratification of AD and clinically suspected 4R-tauopathies.
