Age and sex impact plasma NFL and t-Tau trajectories in individuals with subjective memory complaints: a 3-year follow-up study.

Alzheimer Disease Amyloid beta-Peptides Biomarkers Cognitive Dysfunction Female Follow-Up Studies Humans Male Neurofilament Proteins tau Proteins
Alzheimer’s disease Biomarkers Mild cognitive impairment Neurofilament light chain Subjective memory complainers Tau

Journal

Alzheimer's research & therapy
ISSN: 1758-9193
Titre abrégé: Alzheimers Res Ther
Pays: England
ID NLM: 101511643

Informations de publication

Date de publication:
12 11 2020
Historique:
received: 18 05 2020
accepted: 12 10 2020
entrez: 13 11 2020
pubmed: 14 11 2020
medline: 25 6 2021
Statut: epublish

Résumé

Plasma neurofilament light (NFL) and total Tau (t-Tau) proteins are candidate biomarkers for early stages of Alzheimer's disease (AD). The impact of biological factors on their plasma concentrations in individuals with subjective memory complaints (SMC) has been poorly explored. We longitudinally investigate the effect of sex, age, APOE ε4 allele, comorbidities, brain amyloid-β (Aβ) burden, and cognitive scores on plasma NFL and t-Tau concentrations in cognitively healthy individuals with SMC, a condition associated with AD development. Three hundred sixteen and 79 individuals, respectively, have baseline and three-time point assessments (at baseline, 1-year, and 3-year follow-up) of the two biomarkers. Plasma biomarkers were measured with an ultrasensitive assay in a mono-center cohort (INSIGHT-preAD study). We show an effect of age on plasma NFL, with women having a higher increase of plasma t-Tau concentrations compared to men, over time. The APOE ε4 allele does not affect the biomarker concentrations while plasma vitamin B12 deficiency is associated with higher plasma t-Tau concentrations. Both biomarkers are correlated and increase over time. Baseline NFL is related to the rate of Aβ deposition at 2-year follow-up in the left-posterior cingulate and the inferior parietal gyri. Baseline plasma NFL and the rate of change of plasma t-Tau are inversely associated with cognitive score. We find that plasma NFL and t-Tau longitudinal trajectories are affected by age and female sex, respectively, in SMC individuals. Exploring the influence of biological variables on AD biomarkers is crucial for their clinical validation in blood.

Sections du résumé

BACKGROUND
Plasma neurofilament light (NFL) and total Tau (t-Tau) proteins are candidate biomarkers for early stages of Alzheimer's disease (AD). The impact of biological factors on their plasma concentrations in individuals with subjective memory complaints (SMC) has been poorly explored. We longitudinally investigate the effect of sex, age, APOE ε4 allele, comorbidities, brain amyloid-β (Aβ) burden, and cognitive scores on plasma NFL and t-Tau concentrations in cognitively healthy individuals with SMC, a condition associated with AD development.
METHODS
Three hundred sixteen and 79 individuals, respectively, have baseline and three-time point assessments (at baseline, 1-year, and 3-year follow-up) of the two biomarkers. Plasma biomarkers were measured with an ultrasensitive assay in a mono-center cohort (INSIGHT-preAD study).
RESULTS
We show an effect of age on plasma NFL, with women having a higher increase of plasma t-Tau concentrations compared to men, over time. The APOE ε4 allele does not affect the biomarker concentrations while plasma vitamin B12 deficiency is associated with higher plasma t-Tau concentrations. Both biomarkers are correlated and increase over time. Baseline NFL is related to the rate of Aβ deposition at 2-year follow-up in the left-posterior cingulate and the inferior parietal gyri. Baseline plasma NFL and the rate of change of plasma t-Tau are inversely associated with cognitive score.
CONCLUSION
We find that plasma NFL and t-Tau longitudinal trajectories are affected by age and female sex, respectively, in SMC individuals. Exploring the influence of biological variables on AD biomarkers is crucial for their clinical validation in blood.

Identifiants

DOI: 10.1186/s13195-020-00704-4 PMID: 33183357 PMC: PMC7663867
pubmed: 33183357
doi: 10.1186/s13195-020-00704-4
pii: 10.1186/s13195-020-00704-4
pmc: PMC7663867
doi:

Substances chimiques

Amyloid beta-Peptides 0
Biomarkers 0
Neurofilament Proteins 0
tau Proteins 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

147

Subventions

Organisme : Medical Research Council
ID : MR/L023784/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P005748/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T04604X/1
Pays : United Kingdom

Investigateurs

Hovagim Bakardjian (H)
Habib Benali (H)
Hugo Bertin (H)
Joel Bonheur (J)
Laurie Boukadida (L)
Nadia Boukerrou (N)
Enrica Cavedo (E)
Patrizia Chiesa (P)
Olivier Colliot (O)
Bruno Dubois (B)
Marion Dubois (M)
Stéphane Epelbaum (S)
Geoffroy Gagliardi (G)
Remy Genthon (R)
Marie-Odile Habert (MO)
Harald Hampel (H)
Marion Houot (M)
Aurélie Kas (A)
Foudil Lamari (F)
Marcel Levy (M)
Simone Lista (S)
Christiane Metzinger (C)
Fanny Mochel (F)
Francis Nyasse (F)
Catherine Poisson (C)
Marie-Claude Potier (MC)
Marie Revillon (M)
Antonio Santos (A)
Katia Santos Andrade (KS)
Marine Sole (M)
Mohmed Surtee (M)
Michel Thiebaut de Schotten (MT)
Andrea Vergallo (A)
Nadjia Younsi (N)
Mohammad Afshar (M)
Lisi Flores Aguilar (LF)
Leyla Akman-Anderson (L)
Joaquín Arenas (J)
Jesús Ávila (J)
Claudio Babiloni (C)
Filippo Baldacci (F)
Richard Batrla (R)
Norbert Benda (N)
Keith L Black (KL)
Arun L W Bokde (ALW)
Ubaldo Bonuccelli (U)
Karl Broich (K)
Francesco Cacciola (F)
Filippo Caraci (F)
Giuseppe Caruso (G)
Juan Castrillo (J)
Enrica Cavedo (E)
Roberto Ceravolo (R)
Patrizia A Chiesa (PA)
Massimo Corbo (M)
Jean-Christophe Corvol (JC)
Augusto Claudio (A)
Jeffrey L Cummings (JL)
Herman Depypere (H)
Bruno Dubois (B)
Andrea Duggento (A)
Enzo Emanuele (E)
Valentina Escott-Price (V)
Howard Federoff (H)
Maria Teresa Ferretti (MT)
Massimo Fiandaca (M)
Richard A Frank (RA)
Francesco Garaci (F)
Hugo Geerts (H)
Ezio Giacobini (E)
Filippo S Giorgi (FS)
Edward J Goetzl (EJ)
Manuela Graziani (M)
Marion Haberkamp (M)
Marie-Odile Habert (MO)
Britta Hänisch (B)
Harald Hampel (H)
Karl Herholz (K)
Felix Hernandez (F)
Bruno P Imbimbo (BP)
Dimitrios Kapogiannis (D)
Eric Karran (E)
Steven J Kiddle (SJ)
Seung H Kim (SH)
Yosef Koronyo (Y)
Maya Koronyo-Hamaoui (M)
Todd Langevin (T)
Stéphane Lehéricy (S)
Pablo Lemercier (P)
Simone Lista (S)
Francisco Llavero (F)
Jean Lorenceau (J)
Alejandro Lucía (A)
Dalila Mango (D)
Mark Mapstone (M)
Christian Neri (C)
Robert Nisticò (R)
Sid E O'Bryant (SE)
Giovanni Palermo (G)
George Perry (G)
Craig Ritchie (C)
Simone Rossi (S)
Amira Saidi (A)
Emiliano Santarnecchi (E)
Lon S Schneider (LS)
Olaf Sporns (O)
Nicola Toschi (N)
Pedro L Valenzuela (PL)
Bruno Vellas (B)
Steven R Verdooner (SR)
Andrea Vergallo (A)
Nicolas Villain (N)
Kelly Virecoulon Giudici (K)
Mark Watling (M)
Lindsay A Welikovitch (LA)
Janet Woodcock (J)
Erfan Younesi (E)
José L Zugaza (JL)

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Auteurs

Filippo Baldacci (F)

Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, F-75013, Paris, France. filippo.baldacci@unipi.it.
Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56125, Pisa, Italy. filippo.baldacci@unipi.it.
ORCID: 0000-0002-8752-0556

Simone Lista (S)

Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, F-75013, Paris, France.
Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l'hôpital, F-75013, Paris, France.
Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, Institute of Memory and Alzheimer's Disease (IM2A), F-75013, Paris, France.

Maria Laura Manca (ML)

Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56125, Pisa, Italy.
Department of Mathematics, University of Pisa, Pisa, Italy.

Patrizia A Chiesa (PA)

Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, F-75013, Paris, France.
Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l'hôpital, F-75013, Paris, France.
Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, Institute of Memory and Alzheimer's Disease (IM2A), F-75013, Paris, France.

Enrica Cavedo (E)

Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, F-75013, Paris, France.
Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l'hôpital, F-75013, Paris, France.
Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, Institute of Memory and Alzheimer's Disease (IM2A), F-75013, Paris, France.
Qynapse, Paris, France.

Pablo Lemercier (P)

Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, F-75013, Paris, France.
Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l'hôpital, F-75013, Paris, France.
Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, Institute of Memory and Alzheimer's Disease (IM2A), F-75013, Paris, France.

Henrik Zetterberg (H)

Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
UK Dementia Research Institute, London, UK.

Kaj Blennow (K)

Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.

Marie-Odile Habert (MO)

Laboratoire d'Imagerie Biomédicale, Sorbonne University, CNRS, INSERM, F-75013, Paris, France.
Centre pour l'Acquisition et le Traitement des Images (www.cati-neuroimaging.com), Paris, France.
AP-HP, Hôpital Pitié-Salpêtrière, Département de Médecine Nucléaire, F-75013, Paris, France.

Marie Claude Potier (MC)

ICM Institut du Cerveau et de la Moelle épinière, CNRS UMR7225, INSERM U1127, UPMC, Hôpital de la Pitié-Salpêtrière, 47 Bd de l'Hôpital, F-75013, Paris, France.

Bruno Dubois (B)

Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, F-75013, Paris, France.
Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l'hôpital, F-75013, Paris, France.
Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, Institute of Memory and Alzheimer's Disease (IM2A), F-75013, Paris, France.

Andrea Vergallo (A)

Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, F-75013, Paris, France.

Harald Hampel (H)

Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, F-75013, Paris, France.

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Classifications MeSH

questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Age and sex impact plasma NFL and t-Tau...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Peptides bêta-amyloïdes › Age and sex impact plasma NFL and t-Tau...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Age and sex impact plasma NFL and t-Tau...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Troubles de la cognition › Dysfonctionnement cognitif › Age and sex impact plasma NFL and t-Tau...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études de suivi › Age and sex impact plasma NFL and t-Tau...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Age and sex impact plasma NFL and t-Tau...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines neurofilamenteuses › Age and sex impact plasma NFL and t-Tau...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines associées aux microtubules › Protéines tau › Age and sex impact plasma NFL and t-Tau...