%0 Journal Article
%T Diagnostic performance of plasma pTau217, pTau181, Aβ1-42 and Aβ1-40 in the LUMIPULSE automated platform for the detection of Alzheimer disease.
%A Arranz J
%A Zhu N
%A Rubio-Guerra S
%A Rodríguez-Baz Í
%A Ferrer R
%A Carmona-Iragui M
%A Barroeta I
%A Illán-Gala I
%A Santos-Santos M
%A Fortea J
%A Lleó A
%A Tondo M
%A Alcolea D
%J Alzheimers Res Ther
%V 16
%N 1
%D 2024 Jun 26
%M 38926773
暂无%R 10.1186/s13195-024-01513-9
%X BACKGROUND: 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.
METHODS: 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 Aβ1-42/Aβ1-40 ratio. Plasma pTau217, pTau181, Aβ1-42 and Aβ1-40 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 Aβ1-42/Aβ1-40 ratio. We analyzed the concordance of pTau217 with CSF amyloidosis.
RESULTS: Plasma pTau217 and pTau181 concentration were higher in A + than A- while the plasma Aβ1-42/Aβ1-40 ratio was lower in A + compared to A-. pTau181 and the Aβ1-42/Aβ1-40 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 pTau217, and 0.88 (95% CI 0.84-0.92) for both pTau181 and Aβ1-42/Aβ1-40. Chronic kidney disease (CKD) was related to increased plasma biomarker concentrations, but ratios were less affected. Plasma pTau217 had the highest fold change (× 3.2) and showed high predictive capability in discriminating A + from A-, having 4-7% misclassification rate. The global accuracy of plasma pTau217 using a two-threshold approach was robust in symptomatic groups, exceeding 90%.
CONCLUSIONS: The evaluation of blood biomarkers on an automated platform exhibited high diagnostic accuracy for AD pathophysiology, and pTau217 showed excellent diagnostic accuracy to identify participants with AD in a consecutive sample representing the routine clinical practice in a specialized memory unit.