Diagnostic performance of plasma Aβ1-42, Aβ1-40 and pTau181 in the LUMIPULSE automated platform for the detection of Alzheimer disease

BACKGROUND: Recently-developed blood markers for Alzheimer's (AD) detection have high accuracy but usually require ultra-sensitive analytic tools not commonly available in clinical laboratories. METHODS: We analyzed plasma samples from 367 consecutive participants in the SPIN cohort, comprising 302 euploid participants (67 cognitively unimpaired, 136 participants with mild cognitive impairment, and 99 with dementia) and 65 with Down Syndrome (46 non-demented and 19 with AD dementia). Participants were classified according to CSF biomarkers status using the AT(N) system. Plasma AB1-42, AB1-40 and pTau181 were measured in the fully-automated LUMIPULSE platform. We used ANOVA to compare plasma biomarkers concentrations between AT(N) groups, evaluated Spearman's correlation between plasma and CSF and performed ROC analyses to assess their diagnostic accuracy to detect AD. RESULTS: Plasma pTau181 concentration was higher in A+T+ than A+T- and A-T-, and in A+T- and A-T+ than A-T[ndash]. The plasma AB1-42/AB1-40 ratio was lower in A+T+ and A+T- compared to A-T-. pTau181 and the AB1-42/AB1-40 ratio showed moderate correlation between plasma and CSF (Rho=0.66 and 0.65, respectively). The areas under the ROC curve (AUC) to discriminate A+T+ from A-T- participants were 0.91 for pTau181 and 0.86 for AB1-42/AB1-40. The combination of both measures yielded an AUC=0.94. Chronic kidney disease (CKD) was related to increased plasma biomarker concentrations, but ratios were not significantly affected. CONCLUSION: The feasibility and performance of plasma-based biomarker measurements on an automated platform showed high diagnostic accuracy and hold great promise for the diagnostic process of AD.