Diagnostic performance of plasma pTau 217, pTau 181, Aβ 1-42 and Aβ 1-40 in the LUMIPULSE automated platform for the detection of Alzheimer disease

Abstract

Background: Recently developed blood markers for Alzheimer's disease (AD) detection have high accuracy but usually require ultra-sensitive analytic tools not commonly available in clinical laboratories, and their performance in clinical practice is unknown.

Methods: We analyzed plasma samples from 290 consecutive participants that underwent lumbar puncture in routine clinical practice in a specialized memory clinic (66 cognitively unimpaired, 130 participants with mild cognitive impairment, and 94 with dementia). Participants were classified as amyloid positive (A+) or negative (A-) according to CSF Aβ_1-42/Aβ_1-40 ratio. Plasma pTau₂₁₇, pTau₁₈₁, Aβ_1-42 and Aβ_1-40 were measured in the fully-automated LUMIPULSE platform. We used linear regression to compare plasma biomarkers concentrations between A + and A- groups, evaluated Spearman's correlation between plasma and CSF and performed ROC analyses to assess their diagnostic accuracy to detect brain amyloidosis as determined by CSF Aβ_1-42/Aβ_1-40 ratio. We analyzed the potential of pTau₂₁₇ to predict amyloidosis in CSF.

Results: Plasma pTau₂₁₇ and pTau₁₈₁ concentration were higher in A + than A- while the plasma Aβ_1-42/Aβ_1-40 ratio was lower in A + compared to A-. pTau₁₈₁ and the Aβ_1-42/Aβ_1-40 ratio showed moderate correlation between plasma and CSF (Rho = 0.66 and 0.69, respectively). The areas under the ROC curve to discriminate A + from A- participants were 0.94 (95% CI 0.92-0.97) for pTau₂₁₇, and 0.88 (95% CI 0.84-0.92) for both pTau₁₈₁ and Aβ_1-42/Aβ_1-40. Chronic kidney disease (CKD) was related to increased plasma biomarker concentrations, but ratios were less affected. Plasma pTau₂₁₇ had the highest fold change (x4.2) and showed high predictive capability in discriminating A + from A-, having 4-7% misclassification rate. The global accuracy of plasma pTau₂₁₇ using a two-threshold approach was robust in symptomatic groups, exceeding 90%.

Conclusion: The evaluation of blood biomarkers on an automated platform exhibited high diagnostic accuracy for AD pathophysiology, and pTau₂₁₇ showed excellent diagnostic accuracy to identify participants with AD in a consecutive sample representing the routine clinical practice in a specialized memory unit.

Keywords: Alzheimer; Amyloid; Biomarkers; Blood; Plasma; Tau.