P1‐290: CONCORDANCE BETWEEN IN VIVO AMYLOID IMAGING AND CSF AB 1‐42 AND TOTAL TAU MEASURED BY THE AUTOMATED LUMIPULSE ® G ASSAY PLATFORM
Alzheimer's & Dementia(2006)
Abstract
As biomarkers are increasingly being used as screening, target engagement, and/or outcome measures in clinical trials, automated assay platforms are being developed to optimize analytical performance. Validation of the clinicopathologic utility of such assays is critical for bringing such assays into the clinical space. Thus, we evaluated the correspondence between CSF Ab1-42 and total tau measured with the automated LUMIPULSE G1200 platform, the manual INNOTEST® ELISAs, and in vivo b-amyloid positron emission tomography (PET). CSF samples from 198 participants at the Knight Alzheimer's Disease Research Center at Washington University who underwent amyloid imaging with Pittsburgh Compound B (PIB) within 12 months of CSF collection were analyzed by the automated Lumipulse G β-Amyloid 1-42 and Total Tau assays and manual INNOTEST β-Amyloid(1-42), β-Amyloid(1-40), and hTau assays (Fujirebio Europe). Values for each biomarker and ratios of Aβ1-42/Aβ1-40 and Tau/Aβ1-42 that corresponded best to PIB-positivity (SUVR >1.42) were determined using receiver operating characteristic (ROC) analyses. Cutoff values with the highest Youden index (maximizing sensitivity and specificity) were established for all measures, and optimal concordance at these cutoffs were determined using area under the ROC curve (AUC) analyses. Lumipulse and INNOTEST assays were positively correlated (Ab1-42 Spearman r=0.834; Tau r=0.858, p's<0.0001). Within-sample (n=5-7) reproducibility of a common CSF sample was high (% coefficients of variation [%CV]: Lumipulse G β-Amyloid 1-42 [3.9%]; INNOTEST Ab1-42[5.4%]; INNOTEST Ab1-40[9.8%]; Lumipulse Total Tau [1.6%]; INNOTEST hTau [1.8%]). As expected, CSF Ab1-42 discriminated PIB-positive (n=50) from PIB-negative (n=148) individuals better than Ab1-40 (Lumipulse Ab1-42 AUC=0.83[95% CI, 0.77-0.89]; INNOTEST Ab1-42 AUC=0.88[0.83-0.94]; INNOTEST Ab1-40 AUC=0.57[0.48-0.67]). The Tau assays also discriminated between PIB groups (Lumipulse AUC=0.82[0.76-0.89]; INNOTEST AUC=0.86[0.80-0.92]). When in a ratio with INNOTEST Ab1-40, each Ab1-42 measure outperformed the single Ab1-42 value (Lumipulse Ab1-42/INNOTEST Ab1-40 AUC=0.91[0.85-0.96]; INNOTEST Ab1-42/INNOTEST Ab1-40 AUC=0.88[0.82-0.94]). Furthermore, the Tau/Ab1-42 ratios performed the best for PIB discrimination (Lumipulse AUC=0.94[0.91-0.97]; INNOTEST AUC=0.96[0.94-0.99]). The automated Lumipulse G assays for Ab1-42 and Total Tau showed excellent within-sample reproducibility (%CV<4%) and performed well in discriminating amyloid groups (AUCs=0.82-0.83), especially when put into a ratio (AUC=0.94). These ratios may be useful for enrollment of amyloid-positive individuals into clinical trials.
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Key words
amyloid imaging,total tau
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