Diagnostic performance of plasma Aβ_1-42, Aβ_1-40and pTau₁₈₁in the LUMIPULSE automated platform for the detection of Alzheimer disease

Abstract

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.

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

“… 18 A recent report on the Lumipulse Aβ42/40 immunoassay reported an AUC of 0.86 when using abnormal/normal CSF biomarker results as the outcome measure. 24 In agreement with prior reports, the accuracy for detecting amyloid pathology for the Simoa assay was the lowest in our study cohort (AUC of 0.57). Previous studies have reported AUCs for the Simoa assay ranging from 0.62 to 0.78; with a weighted average AUC of 0.69 across 10 cohorts.…”

“…reported a plasma AUC of 0.91 to distinguish individuals exhibiting both amyloid and tau pathology from amyloid and tau negative individuals compared to CSF biomarkers. 24 …”

Plasma p-tau217 in Alzheimer’s disease: Lumipulse and ALZpath SIMOA head-to-head comparison

“…For Lumipulse p-tau217, only one preliminary study suggested a high discrimination accuracy for AD diagnosis, thought without a head-to-head comparison available to date. 20 Despite the growing number of unpublished data available, there is an urgent need for high quality technical and clinical validation of newly developed p-tau217 markers.…”