Performance of the Lumipulse plasma Aβ42/40 and pTau181 immunoassays in the detection of amyloid pathology

INTRODUCTION: This study evaluated the performance of the Lumipulse plasma beta-amyloid (Aβ) 42/40 and pTau181 compared to other assays to detect an abnormal amyloid-positron emission tomography (PET). METHODS: Plasma samples from cognitively unimpaired (N = 179) and MCI/AD dementia (N = 36) individuals were retrospectively evaluated. Plasma Aβ42/40 and pTau181 were measured using the Lumipulse and Simoa immunoassays. An immunoprecipitation mass spectrometry (IP-MS) assay for plasma Aβ42/40 was also evaluated. Amyloid-PET status was the outcome measure. RESULTS: Lumipulse and IP-MS Aβ42/40 exhibited the highest diagnostic accuracy for detecting an abnormal amyloid-PET (areas under the curve [AUCs] of 0.81 and 0.84, respectively). The Lumipulse and Simoa pTau181 assays exhibited lower performance (AUCs of 0.74 and 0.72, respectively). The Simoa Aβ42/40 assay demonstrated the lowest diagnostic accuracy (AUC 0.57). Combining Aβ42/40 and pTau181 did not significantly improve performance over Aβ42/40 alone for Lumipulse (AUC 0.83) or over pTau181 alone for Simoa (AUC 0.71). DISCUSSION: The Lumipulse Aβ42/40 assay showed similar performance to the IP-MS Aβ42/40 assay for detection of an abnormal amyloid-PET; and both assays performed better than the two p-tau181 immunoassays. The Simoa Aβ42/Aβ40 assay was the least accurate at predicting an abnormal amyloid-PET status. Highlights: Lumipulse plasma Aβ42/Aβ40 AUC for abnormal amyloid-PET detection was 0.81. This performance was comparable to previously reported IP-MS and higher than Simoa. Performance of Alzheimer's disease blood biomarkers varies between assays.