Methodological approaches to account for assay changes in longitudinal biomarker analysis: insights from Alzheimer’s blood biomarkers in the MEMENTO cohort

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2026年6月10日

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Vincent Bouteloup,
Cécile Proust-Lima,
Isabelle Pellegrin,
Andrea Boizard-Moracchini,
Maëva Roy,
Geneviève Chêne,
Vincent Planche,
Carole Dufouil,
Michèle Allard,
Sara Amroun,
Katia Andrade,
Marion Andro,
Daniela Andruita,
Mariam Annan,
Cédric Annweiler,
Pierre Anthony,
Marine Marine,
Christine Astier,
Alexandre Augier,
Nicolas Auguste,
Sophie Auriacombe,
Clément Aveneau,
John Avet,
Carole Azuar,
Laurent Laurent,
Olivier Bailon,
Anna-Chloe Balageas,
Adeline Bannier,
Fabrice-Guy Barral,
Jean Barre,
Marie-Odile Barrellon,
Nicolas Bassiere,
Catherine Bayle,
Olivier Beauchet,
Emilie Beaufils,
Michèle BECKER Schneider,
Yannick Bejot,
Catherine Belin,
Jérémie Belin,
Samia Belkacem,
Serge Belliard,
Douraied Ben Salem,
Marie Benaiteau,
Athanase Benetos,
Karim Bennys,
Alexandre Berger,
Alina Berriolo Riedinger,
François Bertin Hugault,
Catherine Beze,
Julien Biberon,
Theophile Bieth,
Irina Bilubas,
Frédéric Frédéric,
Jérôme Bohatier,
Stéphanie Bombois,
Yasmina Boudali,
Clémence Boully,
Isabelle Bourdel Marchasson,
Claire Boutet,
Claire Boutoleau Bretonniere,
Bruno Bouvel,
Serge Bracard,
Antoine Brangier,
Pierre-Yves Brillet,
Jean-Marc Bugnicourt,
Aurélie Buisson,
Laure Caillard,
Maria Callejo Plazas,
Edouard Caltabellotta,
Fabienne Calvas,
Agnès Camus,
Vincent Camus,
Sandrine Canaple,
Jasmine Carlier,
Antoine Carpentier,
Pascaline Cassagnaud,
Frédérique Castapatry,
Hélène Catala,
Mathieu Ceccaldi,
Pierre Celsis,
LuAuthorNameine Chamard,
Christine Champion,
Anne Chanwakilian,
Edouard Chaussade,
Sophie Chauvelier,
Valérie Chauvire,
Adrien Chavent,
Cécile Chazalon,
Samia Cheriet,
Mathilde Choquer,
Marie Chupin,
Béatrice Claise,
Henri de Clermont-Gallerande,
Julia Coarelli,
Emmanuel Cognat,
Lora Cohen,
Adrien Cohen,
Emmanuelle Comps,
Marie-Helène Coste,
Jean-Philippe Cottier,
François Cotton,
Mathieu Coulongeat,
Hélène Courtemanche,
Anne Courtois,
Olivier-François Couturier,
Pascale Cowppli Bony,
Véronique Cressot,
Benjamin Cretin,
Sofia Da Silva,
Keren Danaila,
Danaila Darcourt,
Jean-François Dartigues,
Ana-Maria Dascalita,
Sophie Dautricourt,
Renaud David,
Kenny David-Chher,
Henri De Clermont,
Astrid De Liege,
Arnaud Decamps,
Marielle Decousus,
Isabelle Defouilloy,
Bertrand Degos,
Christine Delmaire,
Benoit Delpont,
Julien Delrieu,
Rochanak Delsol,
Catherine Demuynck,
Antoine Denis,
Vincent Deramecourt,
Thomas Desmidt,
Agnès Devendeville,
Mira Didic,
Giulia Diemert,
Elsa Dionet,
Maritchu Doireau,
Jennyfer Doridian,
Patrice Douillet,
Foucaud Du Boisgueheneuc,
Delphine Dubail,
Amandine Dubois,
Bruno Dubois,
Maria Dubos,
Laure Ducroq Ducastaing,
Frédérique Dugny,
Elsa Dumont Pougnier,
Julien Dumurgier,
Diane Dupuy,
Alberto Duran Pena,
Emmanuelle Duron,
Guillaume Duval,
Coline Duwicquet,
Inna Dygai Cochet,
Stéphane Epelbaum,
Sandrine Estivin Kochowski,
Frédérique Etcharry Bouyx,
Eric Ettore,
Karim Farid,
Olivier Felician,
Philippe Fernandez,
Nathalie Fievet,
Marie Floccia,
Pacôme Fosse,
Alexandra Foubert Samier,
Gonzague Foucault,
Isabelle Franck,
Denis Frederico,
Audrey Gabelle,
Monique Galitzky,
Céline Gallazzini Crepin,
Radka Gantcheva,
Isabelle Gantois,
Laurence Garbarg Chenon,
Béatrice Garcin,
Antoine Garnier Crussard,
Sinead Gaubert,
Guillaume Gautier,
Remy Genthon,
Armelle Gentric,
Fleur Gerard,
Emmanuel Gerardin,
Claire Gervais,
Jean-Claude Getenet,
Salim Gherabli,
Nadine Girard,
Chantal Girtanner,
Valérie Gissot,
Philippe Goas,
Olivier Godefroy,
Joêlle Goldberg,
Anna Goncalves,
Mathilde Graber,
Daniel Gruker,
Eric Guedj,
Hélène Guepet,
Claude Gueriot,
Mohamed Guernou,
Yves Guilhermet,
Lucie Guyant Marechal,
Marie-Odile Habert,
Sophie Haffen,
Yasmine Hammamouche,
Bernadette Hanesse,
Didier Hannequin,
Olivier Hanon,
Sandrine Harston,
Fabien Hauw,
Fanny Hennekinne,
Intza Hernandorena,
Caroline Hommet,
Claude Hossein Foucher,
Claire Hourregue,
Sophie Huby,
Jacques Hugon,
Laurence Hugonot Diener,
Agnès Jacquin Piques,
Hariniaina Jailany,
Isabelle Jalenques,
Virginie Jannou,
Caroline Jardin,
Betty Jean,
Joanne Jenn,
Laure Joly,
Thérèse Jonveaux,
Adrien Julian,
Anna Kearney Schwarz,
Antony Kelly,
Lena Kermanac,
Nathalie Keromnes,
Catia Khoumri,
Maya Kilani,
Laure Koch Caillard,
Lejla Koric,
Alexandre Krainik,
Pierre Krolak Salmon,
Carine Labat Bezeaud,
Florian Labouree,
Valentina Lacorte,
Françoise Lala,
Chantal Lamy,
Hélène-Marie Lanoiselee,
Cyrille Launay,
Marie-Christine Laurain,
Brice Laurens,
Bernard Laurent,
Raphael Le Bouc,
Maxime Le Floch,
Julien Le Marec,
Pauline Le Squere,
Thibaud Lebouvier,
Claire Leclercq,
Guillaume Legrand,
Stéphane Lehericy,
Hermine Lenoir,
Thomas Leonard,
Victoire Leroy,
Constance Lesoil,
Marcel Levy,
Richard Levy,
Stéphanie Libercier,
Jocelyne Loison,
Adrien Lorette,
David Lussato,
Marie-Anne Mackowiak Cordoliani,
Christophe Magnier,
Eloi Magnin,
Zaza Makaroff,
Patrick Manckoundia,
Jean-François Mangin,
Athina Marantidou,
Isabelle Marcet,
Cécilia Marelli,
Sophie Marilier,
Aurélie Martin,
Idalie Martin,
Géraldine Martin Gaujard,
Catherine Martin Hunyadi,
Olivier Martinaud,
Leyla Mateus Hamdan,
Aude Maurousset,
Julie Mazoyer,
Antonio Melo Dos Santos,
Pierre Menager,
Danielle Mestas,
Hélène Meytadier,
Jean-Marc Michel,
Agnès Michon,
Raffaella Migliaccio,
Pascal Millet,
Sophie Mohr,
Elisabeth Molinier,
Karl Mondon,
Marie Mongin,
Christophe Moog,
Olivier Moreaud,
Pierre-Emmanuel Morel,
Charline Morillon,
Florian Morin,
Alexandre Morin,
Capucine Mouthon Reignier,
Aurélie Mouton,
Esteban Munoz,
Mariano Musacchio,
Nassima Nezzal Salem,
Georges Niewiadomski,
Guillaume Nivaggioni,
Michel Nonent,
Romain Ordonez,
Jean-Marc Orgogozo,
Galdric Orvoen,
Marie Otekpo,
Pierre-Jean Ousset,
Marc Paccalin,
Amandine Pallardy,
Claire Paquet,
Pierre-Yves Pare,
Jérémie Pariente,
Anne Pasco,
Florence Pasquier,
Cécile Pays,
Isabelle Pellegrin,
Bertille Perin,
Jérémie Perisse,
Benoit Pernot,
Julie Peron,
Christine Perret Guillaume,
Xavier de Petigny,
Nathalie Philippi,
Candice Picard,
Jean-Baptiste Pinaquy,
Geneviève Pinganaud,
Vincent Planche,
Matthieu Plichart,
Gabriel Pop,
Laura Popiteau,
Aurélia Poujois,
Michèle Puel,
Mathieu Queneau,
Solène Querellou,
Valérie Quipourt,
Chloé Rachez,
Franck Rachilas,
Marie Rafiq,
Muriel Rainfray,
Alix Ravier,
Micheline Razzouk Cadet,
Frédéric Ricolfi,
Anne-Sophie Rigaud,
Hélène Riviere,
Philippe Robert,
Hélène Robin Ismer,
Mathieu Rodallec,
Adeline Rollin Sillaire,
Olivier Rouaud,
Caroline Roubaud,
Isabelle Rouch,
Carole Roue Jagot,
Julie Roux,
Juliette Sabourault,
Guillaume Sacco,
Alicia Sanchez,
Maria-Joao Santiago Ribeiro,
Dario Saracino,
Alain Sarciron,
Nathalie Sastre Hengan,
Kevin Sautret,
Mathilde Sauvee,
Christian Scheiber,
Frédéric Scholastique,
François Sellal,
Amélie Serra,
Marie-Laure Seux,
Isabela Shin Ike,
Nathalie Simeoni,
Bernard Songy,
Zouina Talbi,
Jean-Yves Tanguy,
Michael Taroux,
Marc Teichmann,
Catherine Terrat,
Jamila Thabet,
Claire Thalamas,
Catherine Thomas Anterion,
Serge Timsit,
François Tison,
Eléonore Tollard,
Anne-Marie Tricoire,
Anne-Cécile Troussiere,
Renata Ursu,
Olga Uspenskaya,
Pierre Vandel,
Bruno Vellas,
Martine Vercelletto,
Olivier Vercruysse,
Antoine Verger,
Julien Vernaudon,
Bernadette Verrat,
Philippe Viau,
Jean-Sebastien Vidal,
Marie-Neige Videau,
Nicolas Villain,
Timour Vitte,
Agathe Vrillon,
Nathalie Wagemann,
Aziza Waissi Sediq,
David Wallon,
Jing Xie,
Michel Zanca,
Paolo Zanotti Fregonara,
Aline Zarea,
Jean Zinszner

摘要

Background

Longitudinal studies allow the modelling of disease progression through repeated measurement of health outcomes, such as biomarkers. Changes in measurement tools over time, due to logistical or financial constraints, may challenge the statistical modeling of outcome trajectories. This study aims to compare two methods for managing changes in blood biomarkers assays over time, in the context of modeling their longitudinal trajectories.

Methods

We analyzed data from 2299 individuals in the French MEMENTO cohort, focusing on two Alzheimer's disease blood biomarkers: 181-phosphorylated tau (p-tau181) and neurofilament light chain (NfL). Baseline blood samples were quantified using an initial assay kit in 2021, while samples collected at 2- and 4-year follow-ups with updated kits in 2023. Two approaches were applied to derive conversion equations for aligning measurements from the initial to the updated assay: (i) a bridging study, requiring biomarker quantification using both the initial and the updated assay in a subsample of individuals and (ii) Latent Process Models (LPM), which established links between the two assays as measures of the same latent process over age, using biomarker measurements available at the 3 timepoints. Prediction error rates were computed, and biomarker trajectories estimated with linear mixed models according to two variables of interest (education level, cognitive impairment).

Results

Prediction error rates were slightly higher for LPM than for bridging for both NfL and p-tau181. While the two methods yielded similar predictions around the median, discrepancies were observed at the tails of the distribution of the observed values. Longitudinal trajectories showed consistent associations for the variables of interest at baseline and during follow-up for both biomarkers.

Conclusions

LPM provide a feasible and efficient method for managing changes in biomarker quantification assays in longitudinal studies. LPM yields results comparable to traditional bridging studies without requiring additional sample analysis. This approach is particularly advantageous in studies with long-term follow-up, where changes in measurement tools cannot always be avoided, offering a straightforward and resource-efficient solution.