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

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....

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Bibliographic Details
Published in:	Clinical chemistry (Baltimore, Md.) Vol. 69; no. 9; pp. 1072 - 1083
Main Authors:	Lehmann, Sylvain, Schraen-Maschke, Susanna, Vidal, Jean-Sébastien, Delaby, Constance, Blanc, Frédéric, Paquet, Claire, Allinquant, Bernadette, Bombois, Stéphanie, Gabelle, Audrey, Hanon, Olivier
Format:	Journal Article
Language:	English
Published:	England American Association for Clinical Chemistry 01-09-2023
Subjects:	Adiponectin Alzheimer Disease Cognitive Dysfunction Cognitive Dysfunction - diagnosis Human health and pathology Humans Life Sciences Plasma Prospective Studies
Online Access:	Get full text
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0009-9147 1530-8561 1530-8561
DOI:	10.1093/clinchem/hvad103