Head-to-head comparison between plasma ptau-217 and Flortaucipir-PET in amyloid-positive patients with cognitive impairment

Background: Plasma measurements of phosphorylated tau (ptau) have emerged as promising biomarkers for Alzheimer’s disease (AD). Studies have shown strong associations between ptau and tau-PET that are mainly driven by the difference between amyloid-positive and amyloid-negative patients. However, the relationship between ptau and tau-PET is not well characterized within patients with AD. We conducted a head-to-head comparison between plasma ptau-217 and tau-PET in patients at the clinical stage of AD and assessed biomarker relationships with demographic and clinical variables. Methods: Eighty-seven amyloid-positive patients (age=66±10, 48% women) with mild cognitive impairment (n=53) or dementia (n=34) underwent structural MRI, amyloid-PET (11C-PIB), tau-PET (18F-flortaucipir, FTP), Mini-Mental State Examination (MMSE, with 28 patients having longitudinal measures 1.5±0.7 years after baseline) and blood draw within a year. Mean cortical PET-Standardized Uptake Value Ratio (SUVR) were extracted using FreeSurfer5.3. Plasma ptau-217 concentrations were measured using an electrochemiluminescence-based assay on the Meso Scale Discovery platform. Results: Ptau-217 and cortical FTP-SUVR were strongly correlated (r=0.61, p<.001, Figure 1). Younger age and female sex, but not APOE4, were associated with higher ptau-217 and FTP-SUVR (Figure 2). Amyloid-PET levels were mildly associated with FTP-SUVR (r=0.26, p=0.02), not ptau-217 (r=0.10, p=0.36, Figure 2). The relationship between ptau-217 and cortical FTP-SUVR was not modified by age, sex, APOE4, or PIB-PET (interactions: p’s>0.25). In the whole group, ptau-217 was associated with FTP-SUVR in temporo-parietal and dorsal prefrontal cortices (Figure 3A). However, ptau-217-FTP association patterns varied with amyloid burden: in patients with moderate amyloid (<97.7 Centiloids), ptau-217 was more strongly associated with temporal FTP-SUVR whereas associations were stronger in primary cortices in patient with higher amyloid levels (Figure 3B). Cross-sectionally, higher ptau-217 and FTP-SUVR were independently associated with lower MMSE (Table 1; Figure 4A). In separate mixed effect models, higher baseline ptau-217 and FTP-SUVR were associated with more severe longitudinal decline in MMSE (Figure 4B); when both biomarkers were entered in the same model, only FTP-SUVR remained significant (Table 2). Conclusions: In amyloid-PET-positive patients with cognitive deficits, ptau-217 and tau-PET had comparable patterns of association with demographic and clinical variables. However, cross-modal and clinical associations tended to be stronger for tau-PET than ptau-217.