Biomarkers

Background: Tau phosphorylated at threonine 217 (pTau217) is one of the most promising blood-based biomarkers of Alzheimer's disease (AD). This study compares the performance of two plasma pTau217 immunoassays on the Simoa platform for detection of abnormal amyloid-PET.

Method: Plasma samples from 112 individuals without cognitive impairment and 114 with mild cognitive impairment (MCI) or AD related dementia were evaluated. Testing was performed on the Quanterix Simoa® HD-X Analyzer using the ALZpath Simoa® pTau217 and the Simoa® ACC pTau217 (Janssen antibodies) commercial assays. Amyloid-PET imaging was performed using ¹¹C-Pittsburgh Compound B and a standard uptake value ratio (SUVR) cutoff of ≥1.52 (≥25 Centiloid) was used for abnormal (n= 147) vs. normal (n= 79) classification. Passing-Bablok regression analysis and Spearman's correlation coefficient (rho) were used to estimate bias and correlation between the assays, respectively. Correlation of each assay with Amyloid-PET SUVR was evaluated. Amyloid-PET status as the outcome and plasma pTau217 as predictor was used to estimate the area under the receiver operating characteristic (ROC) curve (AUC).

Result: The pTau217 concentrations between the two assays showed an excellent correlation (Spearman's rho= 0.94 [95% CI= 0.93 to 0.96, p<0.0001]). However, the Passing-Bablok regression analysis equation for ALZpath (x-axis) and ACC (y-axis) was y= 0.1324x - 0.0019, showing that measured pTau217 concentrations with the ALZpath assay were higher (∼87%) than with the ACC assay (concentrations ranged 0.057 to 3.5 pg/mL and 0.003 to 0.5 pg/mL, respectively). Correlations between amyloid-PET SUVR and the two pTau217 immunoassays were almost identical with Spearman's rho= 0.70 (95% CI= 0.62 to 0.76, p<0.0001) for ALZpath and 0.69 (95% CI= 0.61 to 0.75, p<0.0001) for ACC. The AUC for detection of an abnormal amyloid-PET among the MCI/AD group was 0.88 (95% CI= 0.81 to 0.95) for ALZpath, and 0.89 (95% CI= 0.83 to 0.96) for ACC.

Conclusion: Analytically, the two Simoa® pTau217 assays correlate well with each other, but results are not interchangeable due to a significant proportional bias. Clinically, the performance of the assays was largely equivalent for the detection of abnormal amyloid-PET by AUC analysis based on their almost identical correlations with amyloid-PET SUVR.