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

BACKGROUNDRecently-developed blood markers for Alzheimers (AD) detection have high accuracy but usually require ultra-sensitive analytic tools not commonly available in clinical laboratories. METHODSWe 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 A{beta}1-42, A{beta}1-40 and pTau181 were measured in the fully-automated LUMIPULSE platform. We used ANOVA to compare plasma biomarkers concentrations between AT(N) groups, evaluated Spearmans correlation between plasma and CSF and performed ROC analyses to assess their diagnostic accuracy to detect AD. RESULTSPlasma pTau181 concentration was higher in A+T+ than A+T- and A-T-, and in A+T- and A-T+ than A-T-. The plasma A{beta}1-42/A{beta}1-40 ratio was lower in A+T+ and A+T- compared to A-T-. pTau181 and the A{beta}1-42/A{beta}1-40 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 A{beta}1-42/A{beta}1-40. 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. CONCLUSIONThe 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. What is already known on this topicBlood biomarkers have shown high accuracy to detect AD pathophysiology. The feasibility of those biomarkers in different platforms and the influence of comorbidities in their concentrations needs to be studied. What this study addsWe analyze the feasibility and diagnostic performance of AD biomarkers measured in a fully-automated platform and assess how comorbidities affect their concentrations. How this study might affect research, practice, or policyThe measurement of plasma AD biomarkers in an automated platform yields high accuracy to detect AD pathophysiology and would be easy to implement. Plasma AD biomarker concentrations are increased in chronic kidney disease, and in this context, the use of ratios would be more reliable.