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

Bouteloup V(1)(2)(3), Proust-Lima C(4), Pellegrin I(5)(6), Boizard-Moracchini A(5), Roy M(5), Chêne G(4)(7), Planche V(#)(8)(9), Dufouil C(#)(4)(7); MEMENTO study group.

Collaborators: Allard M, Amroun S, Andrade K, Andro M, Andruita D, Annan M,
Annweiler C, Anthony P, Marine M, Astier C, Augier A, Auguste N, Auriacombe S,
Aveneau C, Avet J, Azuar C, Laurent L, Bailon O, Balageas AC, Bannier A, Barral
FG, Barre J, Barrellon MO, Bassiere N, Bayle C, Beauchet O, Beaufils E,
Schneider MB, Bejot Y, Belin C, Belin J, Belkacem S, Belliard S, Ben Salem D,
Benaiteau M, Benetos A, Bennys K, Berger A, Berriolo Riedinger A, Bertin Hugault
F, Beze C, Biberon J, Bieth T, Bilubas I, Frédéric F, Bohatier J, Bombois S,
Boudali Y, Boully C, Bourdel Marchasson I, Boutet C, Boutoleau Bretonniere C,
Bouvel B, Bracard S, Brangier A, Brillet PY, Bugnicourt JM, Buisson A, Caillard
L, Callejo Plazas M, Caltabellotta E, Calvas F, Camus A, Camus V, Canaple S,
Carlier J, Carpentier A, Cassagnaud P, Castapatry F, Catala H, Ceccaldi M,
Celsis P, Chamard L, Champion C, Chanwakilian A, Chaussade E, Chauvelier S,
Chauvire V, Chavent A, Chazalon C, Cheriet S, Choquer M, Chupin M, Claise B, de
Clermont-Gallerande H, Coarelli J, Cognat E, Cohen L, Cohen A, Comps E, Coste
MH, Cottier JP, Cotton F, Coulongeat M, Courtemanche H, Courtois A, Couturier
OF, Cowppli Bony P, Cressot V, Cretin B, Da Silva S, Danaila K, Darcourt D,
Dartigues JF, Dascalita AM, Dautricourt S, David R, David-Chher K, De Clermont
H, De Liege A, Decamps A, Decousus M, Defouilloy I, Degos B, Delmaire C, Delpont
B, Delrieu J, Delsol R, Demuynck C, Denis A, Deramecourt V, Desmidt T,
Devendeville A, Didic M, Diemert G, Dionet E, Doireau M, Doridian J, Douillet P,
Du Boisgueheneuc F, Dubail D, Dubois A, Dubois B, Dubos M, Ducroq Ducastaing L,
Dugny F, Dumont Pougnier E, Dumurgier J, Dupuy D, Duran Pena A, Duron E, Duval
G, Duwicquet C, Dygai Cochet I, Epelbaum S, Estivin Kochowski S, Etcharry Bouyx
F, Ettore E, Farid K, Felician O, Fernandez P, Fievet N, Floccia M, Fosse P,
Foubert Samier A, Foucault G, Franck I, Frederico D, Gabelle A, Galitzky M,
Gallazzini Crepin C, Gantcheva R, Gantois I, Garbarg Chenon L, Garcin B, Garnier
Crussard A, Gaubert S, Gautier G, Genthon R, Gentric A, Gerard F, Gerardin E,
Gervais C, Getenet JC, Gherabli S, Girard N, Girtanner C, Gissot V, Goas P,
Godefroy O, Goldberg J, Goncalves A, Graber M, Gruker D, Guedj E, Guepet H,
Gueriot C, Guernou M, Guilhermet Y, Guyant Marechal L, Habert MO, Haffen S,
Hammamouche Y, Hanesse B, Hannequin D, Hanon O, Harston S, Hauw F, Hennekinne F,
Hernandorena I, Hommet C, Hossein Foucher C, Hourregue C, Huby S, Hugon J,
Hugonot Diener L, Jacquin Piques A, Jailany H, Jalenques I, Jannou V, Jardin C,
Jean B, Jenn J, Joly L, Jonveaux T, Julian A, Kearney Schwarz A, Kelly A,
Kermanac L, Keromnes N, Khoumri C, Kilani M, Koch Caillard L, Koric L, Krainik
A, Krolak Salmon P, Labat Bezeaud C, Labouree F, Lacorte V, Lala F, Lamy C,
Lanoiselee HM, Launay C, Laurain MC, Laurens B, Laurent B, Le Bouc R, Le Floch
M, Le Marec J, Le Squere P, Lebouvier T, Leclercq C, Legrand G, Lehericy S,
Lenoir H, Leonard T, Leroy V, Lesoil C, Levy M, Levy R, Libercier S, Loison J,
Lorette A, Lussato D, Mackowiak Cordoliani MA, Magnier C, Magnin E, Makaroff Z,
Manckoundia P, Mangin JF, Marantidou A, Marcet I, Marelli C, Marilier S, Martin
A, Martin I, Martin Gaujard G, Martin Hunyadi C, Martinaud O, Mateus Hamdan L,
Maurousset A, Mazoyer J, Melo Dos Santos A, Menager P, Mestas D, Meytadier H,
Michel JM, Michon A, Migliaccio R, Millet P, Mohr S, Molinier E, Mondon K,
Mongin M, Moog C, Moreaud O, Morel PE, Morillon C, Morin F, Morin A, Mouthon
Reignier C, Mouton A, Munoz E, Musacchio M, Nezzal Salem N, Niewiadomski G,
Nivaggioni G, Nonent M, Ordonez R, Orgogozo JM, Orvoen G, Otekpo M, Ousset PJ,
Paccalin M, Pallardy A, Paquet C, Pare PY, Pariente J, Pasco A, Pasquier F, Pays
C, Pellegrin I, Perin B, Perisse J, Pernot B, Peron J, Perret Guillaume C, de
Petigny X, Philippi N, Picard C, Pinaquy JB, Pinganaud G, Planche V, Plichart M,
Pop G, Popiteau L, Poujois A, Puel M, Queneau M, Querellou S, Quipourt V, Rachez
C, Rachilas F, Rafiq M, Rainfray M, Ravier A, Razzouk Cadet M, Ricolfi F, Rigaud
AS, Riviere H, Robert P, Robin Ismer H, Rodallec M, Rollin Sillaire A, Rouaud O,
Roubaud C, Rouch I, Roue Jagot C, Roux J, Sabourault J, Sacco G, Sanchez A,
Santiago Ribeiro MJ, Saracino D, Sarciron A, Sastre Hengan N, Sautret K, Sauvee
M, Scheiber C, Scholastique F, Sellal F, Serra A, Seux ML, Shin Ike I, Simeoni
N, Songy B, Talbi Z, Tanguy JY, Taroux M, Teichmann M, Terrat C, Thabet J,
Thalamas C, Thomas Anterion C, Timsit S, Tison F, Tollard E, Tricoire AM,
Troussiere AC, Ursu R, Uspenskaya O, Vandel P, Vellas B, Vercelletto M,
Vercruysse O, Verger A, Vernaudon J, Verrat B, Viau P, Vidal JS, Videau MN,
Villain N, Vitte T, Vrillon A, Wagemann N, Waissi Sediq A, Wallon D, Xie J,
Zanca M, Zanotti Fregonara P, Zarea A, Zinszner J.

Author information:
(1)University Bordeaux, Inserm, Bordeaux Population Health, UMR1219, Bordeaux,
France. .
(2)CIC 1401 EC, Pôle Santé Publique, CHU de Bordeaux, Bordeaux, France.
.
(3)Bordeaux Population Health, Université de Bordeaux, UMR 1219, Bâtiment ISPED,
146, Rue Léo Saignat, Bordeaux, Cedex, CS61292 33076, France.
.
(4)University Bordeaux, Inserm, Bordeaux Population Health, UMR1219, Bordeaux,
France.
(5)Laboratory of Immunology and Immunogenetics, Resources Biological Center
(CRB), CHU Bordeaux, Bordeaux, France.
(6)University Bordeaux, CNRS, ImmunoConcEpT, UMR 5164, Bordeaux, France.
(7)CIC 1401 EC, Pôle Santé Publique, CHU de Bordeaux, Bordeaux, France.
(8)University Bordeaux, CNRS, Institut Des Maladies Neurodégénératives, UMR
5293, Bordeaux, France.
(9)Pôle de Neurosciences Cliniques, Centre Mémoire de Ressources Et de
Recherche, CHU de Bordeaux, Bordeaux, France.
(#)Contributed equally

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.

© 2026. The Author(s).

DOI: 10.1186/s13195-026-02042-3
PMID: 42265779

Conflict of interest statement: Declarations. Ethics approval and consent to
participate: This study was performed in line with the principles of the
Declaration of Helsinki. The study protocol was approved by the ethics committee
“CPP Sud-Ouest et Outre-Mer III”. All participants enrolled in MEMENTO gave
their informed consent. Competing interests: During the past 3 years, VP was a
local unpaid investigator or sub-investigator for clinical trials granted by
NovoNordisk, Biogen, TauRx Pharmaceuticals, Janssen, Green Valley
Pharmaceuticals and Alector. He received consultant fees for animal studies from
Motac Neuroscience Ltd, outside the submitted work. All other authors have no
competing interest to declare.

Auteurs Bordeaux Neurocampus