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.

Publisher: BioMed Central Ltd Country of Publication: England NLM ID: 101511643 Publication Model: Electronic Cited Medium: Internet ISSN: 1758-9193 (Electronic) NLM ISO Abbreviation: Alzheimers Res Ther Subsets: MEDLINE

Original Publication: [London] : BioMed Central Ltd.

Amyloid beta-Peptides*/blood ; Amyloid beta-Peptides*/cerebrospinal fluid ; Alzheimer Disease*/blood ; Alzheimer Disease*/diagnosis ; Alzheimer Disease*/cerebrospinal fluid ; Peptide Fragments*/blood ; Peptide Fragments*/cerebrospinal fluid ; tau Proteins*/blood ; tau Proteins*/cerebrospinal fluid ; Biomarkers*/blood ; Biomarkers*/cerebrospinal fluid; Humans ; Female ; Male ; Aged ; Middle Aged ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/blood ; Cognitive Dysfunction/cerebrospinal fluid ; Aged, 80 and over ; ROC Curve ; Phosphorylation

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 Aβ 1-42 /Aβ 1-40 ratio. Plasma pTau 217 , pTau 181 , Aβ 1-42 and Aβ 1-40 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 Aβ 1-42 /Aβ 1-40 ratio. We analyzed the concordance of pTau 217 with CSF amyloidosis.
Results: Plasma pTau 217 and pTau 181 concentration were higher in A + than A- while the plasma Aβ 1-42 /Aβ 1-40 ratio was lower in A + compared to A-. pTau 181 and the Aβ 1-42 /Aβ 1-40 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 pTau 217 , and 0.88 (95% CI 0.84-0.92) for both pTau 181 and Aβ 1-42 /Aβ 1-40 . Chronic kidney disease (CKD) was related to increased plasma biomarker concentrations, but ratios were less affected. Plasma pTau 217 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 pTau 217 using a two-threshold approach was robust in symptomatic groups, exceeding 90%.
Conclusion: The evaluation of blood biomarkers on an automated platform exhibited high diagnostic accuracy for AD pathophysiology, and pTau 217 showed excellent diagnostic accuracy to identify participants with AD in a consecutive sample representing the routine clinical practice in a specialized memory unit.
(© 2024. The Author(s).)

Update of: Res Sq. 2023 Dec 13:rs.3.rs-3725688. doi: 10.21203/rs.3.rs-3725688/v1. (PMID: 38168408)
Erratum in: Alzheimers Res Ther. 2024 Jul 27;16(1):168. doi: 10.1186/s13195-024-01538-0. (PMID: 39068457)

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PI17/01896 and AC19/00103to AL Instituto de Salud Carlos III; Juan Rodés Contract (JR20/0018) Instituto de Salud Carlos III; PI18/00164; PI21/00140 Instituto de Salud Carlos III; PI18/00335 to MCI Instituto de Salud Carlos III; 20142610 to AL Fundació la Marató de TV3; PI14/01126, PI17/01019 and PI20/01473 to JF Instituto de Salud Carlos III; RF1 AG061566 United States AG NIA NIH HHS; RF1 AG056850 United States AG NIA NIH HHS; PI18/00435 and INT19/00016 Instituto de Salud Carlos III; PERIS SLT006/17/125 Pla Estratègic de Recerca i Innovació en Salut; Atlantic Fellows for Equity in Brain Health at the Global Brain Health Institute Global Brain Health Institute; R21 AG056974 United States AG NIA NIH HHS; 20141210 to JF Fundació la Marató de TV3; Program 1, Alzheimer Disease to AL Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas; National Institutes of Health (R01AG080470) United States GF NIH HHS; R01 AG080470 United States AG NIA NIH HHS; Alzheimer's Association clinician scientist fellowship (AACSF-22-972945) United States ALZ Alzheimer's Association; Rio Hortega Instituto de Salud Carlos III; NIA grants 1R01AG056850-01A1; R21AG056974; and R01AG061566 to JF United States NH NIH HHS; AACSF-21-850193 United Kingdom ALZS_ Alzheimer's Society; ALZ UK-21-720973 United States ALZ Alzheimer's Association; Juan Rodés contract JR18-00018; Fondo de investigación sanitaria grant PI19/00882 Instituto de Salud Carlos III

Keywords: Alzheimer; Amyloid; Biomarkers; Blood; Plasma; Tau

0 (Amyloid beta-Peptides)
0 (Peptide Fragments)
0 (tau Proteins)
0 (amyloid beta-protein (1-42))
0 (amyloid beta-protein (1-40))
0 (Biomarkers)

Date Created: 20240626 Date Completed: 20240627 Latest Revision: 20240728

20240728

PMC11200993

10.1186/s13195-024-01513-9

38926773