Head-to-Head Comparison of Two Plasma Phospho-tau Assays in Predicting Conversion of Mild Cognitive Impairment to Dementia.


Journal

Clinical chemistry
ISSN: 1530-8561
Titre abrégé: Clin Chem
Pays: England
ID NLM: 9421549

Informations de publication

Date de publication:
01 09 2023
Historique:
received: 07 02 2023
accepted: 06 06 2023
medline: 4 9 2023
pubmed: 1 9 2023
entrez: 1 9 2023
Statut: ppublish

Résumé

Among blood biomarkers, phospho-tau181 (pTau181) is one of the most efficient in detecting Alzheimer disease across its continuum. However, transition from research to routine clinical use will require confirmation of clinical performance in prospective cohorts and evaluation of cofounding factors. Here we tested the Lumipulse assay for plasma pTau181 in mild cognitive impairment (MCI) participants from the Baltazar prospective cohort. We compared the performance of this assay to the corresponding Simoa assay for the prediction of conversion to dementia. We also evaluated the association with various routine blood parameters indicative of comorbidities. Lumipulse and Simoa gave similar results overall, with hazard ratios for conversion to dementia of 3.48 (95% CI, 2.23-5.45) and 3.70 (95%CI, 2.39-5.87), respectively. However, the 2 tests differ somewhat in terms of the patients identified, suggesting that their use may be complementary. When combined with age, sex, and apolipoprotein E (APOE)ε4 status, areas under the curves for conversion detection were 0.736 (95% CI, 0.682-0.791) for Lumipulse and 0.733 (95% CI, 0.679-0.788) for Simoa. Plasma pTau181 was independently associated with renal dysfunction (assessed by creatinine and glomerular filtration) for both assays. Cardiovascular factors (adiponectin and cholesterol), nutritional, and inflammatory markers (total protein content, C-reactive protein) also impacted plasma pTau181 concentration, although more so with the Simoa than with the Lumipulse assay. Plasma pTau181 measured using the fully automated Lumipulse assay performs as well as the Simoa assay for detecting conversion to dementia of MCI patients within 3 years and Lumipulse is less affected by comorbidities. This study suggests a pathway to routine noninvasive in vitro diagnosis-approved testing to contribute to the management of Alzheimer disease. NCT01315639.

Sections du résumé

BACKGROUND
Among blood biomarkers, phospho-tau181 (pTau181) is one of the most efficient in detecting Alzheimer disease across its continuum. However, transition from research to routine clinical use will require confirmation of clinical performance in prospective cohorts and evaluation of cofounding factors.
METHODS
Here we tested the Lumipulse assay for plasma pTau181 in mild cognitive impairment (MCI) participants from the Baltazar prospective cohort. We compared the performance of this assay to the corresponding Simoa assay for the prediction of conversion to dementia. We also evaluated the association with various routine blood parameters indicative of comorbidities.
RESULTS
Lumipulse and Simoa gave similar results overall, with hazard ratios for conversion to dementia of 3.48 (95% CI, 2.23-5.45) and 3.70 (95%CI, 2.39-5.87), respectively. However, the 2 tests differ somewhat in terms of the patients identified, suggesting that their use may be complementary. When combined with age, sex, and apolipoprotein E (APOE)ε4 status, areas under the curves for conversion detection were 0.736 (95% CI, 0.682-0.791) for Lumipulse and 0.733 (95% CI, 0.679-0.788) for Simoa. Plasma pTau181 was independently associated with renal dysfunction (assessed by creatinine and glomerular filtration) for both assays. Cardiovascular factors (adiponectin and cholesterol), nutritional, and inflammatory markers (total protein content, C-reactive protein) also impacted plasma pTau181 concentration, although more so with the Simoa than with the Lumipulse assay.
CONCLUSIONS
Plasma pTau181 measured using the fully automated Lumipulse assay performs as well as the Simoa assay for detecting conversion to dementia of MCI patients within 3 years and Lumipulse is less affected by comorbidities. This study suggests a pathway to routine noninvasive in vitro diagnosis-approved testing to contribute to the management of Alzheimer disease.
CLINICALTRIALS.GOV REGISTRATION NUMBER
NCT01315639.

Identifiants

pubmed: 37654065
pii: 7235402
doi: 10.1093/clinchem/hvad103
doi:

Substances chimiques

Adiponectin 0

Banques de données

ClinicalTrials.gov
['NCT01315639']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1072-1083

Informations de copyright

© American Association for Clinical Chemistry 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Auteurs

Sylvain Lehmann (S)

Univ Montpellier, IRMB CHU de Montpellier, INM INSERM, Montpellier, France.

Susanna Schraen-Maschke (S)

Inserm, CHU Lille, UMR-S-U1172, LiCEND, Lille Neuroscience & Cognition, LabEx DISTALZ, University of Lille, Lille, France.

Jean-Sébastien Vidal (JS)

EA 4468, APHP, Hospital Broca, Memory Resource and Research Centre of de Paris-Broca-Ile de France, Université Paris Cité, Paris, France.

Constance Delaby (C)

Univ Montpellier, IRMB CHU de Montpellier, INM INSERM, Montpellier, France.
Sant Pau Memory Unit, Hospital de la Santa Creu i Sant Pau-Biomedical Research Institute Sant Pau-Universitat Autònoma de Barcelona, Barcelona, Spain.

Frédéric Blanc (F)

CHRU de Strasbourg, Memory Resource and Research Centre of Strasbourg/Colmar, French National Centre for Scientific Research, ICube Laboratory and Fédération de Médecine Translationnelle de Strasbourg, Team Imagerie Multimodale Intégrative en Santé /Neurocrypto, Université de Strasbourg, Strasbourg, France.

Claire Paquet (C)

GHU APHP Nord Lariboisière Fernand Widal, Centre de Neurologie Cognitive, Université Paris Cité, Paris, France.

Bernadette Allinquant (B)

UMR-S1266, Institute of Psychiatry and Neurosciences, Inserm, Université Paris Cité, Paris, France.

Stéphanie Bombois (S)

Inserm, CHU Lille, UMR-S-U1172, LiCEND, Lille Neuroscience & Cognition, LabEx DISTALZ, University of Lille, Lille, France.
Assistance Publique-Hôpitaux de Paris, Département de Neurologie, Centre des Maladies Cognitives et Comportementales, GH Pitié-Salpêtrière, Paris, France.

Audrey Gabelle (A)

Memory Research and Resources Center, Department of Neurology, Inserm INM NeuroPEPs Team, Université de Montpellier, Montpellier, France.

Olivier Hanon (O)

EA 4468, APHP, Hospital Broca, Memory Resource and Research Centre of de Paris-Broca-Ile de France, Université Paris Cité, Paris, France.

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Classifications MeSH