| Autor: |
Ashton, Nicholas J., Molfetta, Guglielmo Di, Brum, Wagner Scheeren, Benedet, Andrea Lessa, Arslan, Burak, Jonaitis, Erin M., Langhough, Rebecca E, Cody, Karly Alex, Betthauser, Tobey J, Hogan, Kirk J., Christian, Bradley T., Rahmouni, Nesrine, Stevenson, Jenna, Montoliu‐Gaya, Laia, Rodriguez, Juan Lantero, Triana‐Baltzer, Gallen, Kolb, Hartmuth C., Vanbrabant, Jeroen, Stoops, Erik, Jeromin, Andreas |
| Zdroj: |
Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2023 Supplement 14, Vol. 19, p1-3, 3p |
| Abstrakt: |
Background: In the last 5 years, immunoassays for the quantification of phosphorylated tau (p‐tau) in blood have proven to accurately identify Alzheimer's disease (AD) pathology with important implications for primary care management and therapeutic trials. Comparisons of p‐tau epitopes (p‐tau181, p‐tau217, p‐tau231) show small differences in diagnostic accuracy, however, often p‐tau217 is preferred, citing its larger fold‐change in symptomatic patients and lower rate of false positives in amyloid‐negative individuals. This study describes the performance of a novel Single molecule array (Simoa) for p‐tau217 (p‐tau217ALZpath) Method: We included 355 participants from Translational Biomarkers in Aging and Dementia (TRIAD) participants, which was representative of the AD continuum. Further, 425 cognitively unimpaired individuals, with longitudinal plasma measures (≤8 years), were included from Wisconsin Registry for Alzheimer's Prevention (WRAP). All plasma samples were measured for ALZpath p‐tau217ALZpath, a validated Simoa assay at the University of Gothenburg, Sweden. In TRIAD, amyloid positivity (A+) was defined as [18F]AZD‐4694 SUVR >1.5 or CSF Aβ42/40 <0.068. In WRAP, A+ was defined by [11C]PiB >1.16. 18F‐MK‐6240 determined tau status (T+) both cohorts (TRIAD, >1.24 SUVR; WRAP, >1.3). Result: In TRIAD, p‐tau217ALZpath determined A+ (AUC = 0.957, 0.935‐978) and T+ (AUC = 0.952, 0.929–0.976) individuals with high accuracy. A sensitivity analysis, including only participants with imaging (amyloid and tau) and CSF biomarkers (p‐tau181, p‐tau205, p‐tau217, Aβ42/40), p‐tau217ALZpath demonstrated equivalent accuracies in determining A+ (Figure 1A) and T+ (Figure 1B) than these high‐performing modalities. In addition, plasma p‐tau217AlzPATH demonstrated a good accuracy to identify T+ from all A+ participants (AUC = 0.839, 0.767‐910). Concentration cut‐points derived in WRAP to identify A+ (>0.676 pg/mL; PPV = 87.2%) and A– (<0.235 pg/mL; NPV = 98.2%) were directly tested in TRIAD with high accuracy (>0.676 pg/mL, PPV = 98.8%; <0.235 pg/mL, NPV = 95.1%. In WRAP, longitudinal analysis (Figure 2) demonstrated that over 8‐years, p‐tau217AlzPATH increased only in A+ individuals and more steeply in A+T+ participants (βestimate = 0.1 pg/mL per year; P<0.0001) compared to A+T‐ (βestimate = 0.022 pg/mL per year, P = 0.0008). Conclusion: The novel p‐tau217ALZpath immunoassay demonstrates high accuracy to determine amyloid and tau pathology across all stages of AD continuum. Clinical cut‐points to identify A+ or A– with high PPV and NPV are directly transferable across cohorts. [ABSTRACT FROM AUTHOR] |
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