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
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. We analyzed plasma samples from 290 consecutive p...
| Authors: | , , , , , , , , , , , , |
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| Format: | article |
| Publication Date: | 2023 |
| Country: | España |
| Institution: | Universitat Autònoma de Barcelona |
| Repository: | Dipòsit Digital de Documents de la UAB |
| Language: | English |
| OAI Identifier: | oai:ddd.uab.cat:307589 |
| Online Access: | https://ddd.uab.cat/record/307589 https://dx.doi.org/urn:doi:10.21203/rs.3.rs-3725688/v1 |
| Access Level: | Open access |
| Keyword: | Plasma Biomarkers Alzheimer Blood Amyloid Tau |
| Summary: | 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. 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/Aβ ratio. Plasma pTau, pTau, Aβ and Aβ 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/Aβ ratio. We analyzed the potential of pTau to predict amyloidosis in CSF. Plasma pTau and pTau concentration were higher in A + than A- while the plasma Aβ/Aβ ratio was lower in A + compared to A-. pTau and the Aβ/Aβ 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 pTau, and 0.88 (95% CI 0.84-0.92) for both pTau and Aβ/Aβ. Chronic kidney disease (CKD) was related to increased plasma biomarker concentrations, but ratios were less affected. Plasma pTau 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 pTau using a two-threshold approach was robust in symptomatic groups, exceeding 90%. The evaluation of blood biomarkers on an automated platform exhibited high diagnostic accuracy for AD pathophysiology, and pTau showed excellent diagnostic accuracy to identify participants with AD in a consecutive sample representing the routine clinical practice in a specialized memory unit. |
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