TY - JOUR
T1 - Age and sex impact plasma NFL and t-Tau trajectories in individuals with subjective memory complaints
T2 - a 3-year follow-up study
AU - for the Alzheimer Precision Medicine Initiative (APMI)
AU - the INSIGHT-preAD study group
AU - Baldacci, Filippo
AU - Lista, Simone
AU - Manca, Maria Laura
AU - Chiesa, Patrizia A.
AU - Cavedo, Enrica
AU - Lemercier, Pablo
AU - Zetterberg, Henrik
AU - Blennow, Kaj
AU - Habert, Marie Odile
AU - Potier, Marie Claude
AU - Dubois, Bruno
AU - Vergallo, Andrea
AU - Hampel, Harald
AU - Bakardjian, Hovagim
AU - Benali, Habib
AU - Bertin, Hugo
AU - Bonheur, Joel
AU - Boukadida, Laurie
AU - Boukerrou, Nadia
AU - Chiesa, Patrizia
AU - Colliot, Olivier
AU - Dubois, Marion
AU - Epelbaum, Stéphane
AU - Gagliardi, Geoffroy
AU - Genthon, Remy
AU - Houot, Marion
AU - Kas, Aurélie
AU - Lamari, Foudil
AU - Levy, Marcel
AU - Metzinger, Christiane
AU - Mochel, Fanny
AU - Nyasse, Francis
AU - Poisson, Catherine
AU - Potier, Marie Claude
AU - Revillon, Marie
AU - Santos, Antonio
AU - Andrade, Katia Santos
AU - Sole, Marine
AU - Surtee, Mohmed
AU - de Schotten, Michel Thiebaut
AU - Younsi, Nadjia
AU - Afshar, Mohammad
AU - Aguilar, Lisi Flores
AU - Akman-Anderson, Leyla
AU - Arenas, Joaquín
AU - Ávila, Jesús
AU - Babiloni, Claudio
AU - Batrla, Richard
AU - Benda, Norbert
AU - O’Bryant, Sid E.
N1 - Funding Information:
The research and this manuscript was part of the translational research program “PHOENIX,” awarded to HH, and administered by the Sorbonne University Foundation and sponsored by la Fondation pour la Recherche sur Alzheimer.
Funding Information:
HZ is a Wallenberg Academy Fellow supported by grants from the Swedish Research Council, the European Research Council, Swedish State Support for Clinical Research (ALFGBG), and the UK Dementia Research Institute at UCL.
Funding Information:
The research and this manuscript was part of the translational research program ?PHOENIX,? awarded to HH, and administered by the Sorbonne University Foundation and sponsored by la Fondation pour la Recherche sur Alzheimer. The study was promoted by INSERM in collaboration with ICM, IHU-A-ICM, and Pfizer and has received support within the ?Investissement d?Avenir? (ANR-10-AIHU-06) French program. The study was promoted in collaboration with the ?CHU de Bordeaux? (coordination CIC EC7), the promoter of Memento cohort, funded by the Foundation Plan-Alzheimer. The study was further supported by AVID/Lilly. CATI is a French neuroimaging platform funded by the French Plan Alzheimer (available at http://cati-neuroimaging.com).
Funding Information:
The study was promoted by INSERM in collaboration with ICM, IHU-A-ICM, and Pfizer and has received support within the “Investissement d’Avenir” (ANR-10-AIHU-06) French program. The study was promoted in collaboration with the “CHU de Bordeaux” (coordination CIC EC7), the promoter of Memento cohort, funded by the Foundation Plan-Alzheimer. The study was further supported by AVID/Lilly.
Funding Information:
CATI is a French neuroimaging platform funded by the French Plan Alzheimer (available at http://cati-neuroimaging.com ). Acknowledgements
Funding Information:
KB holds the Torsten Söderberg Professorship in Medicine at the Royal Swedish Academy of Sciences and is supported by the Swedish Research Council (#2017-00915), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), and a grant (#ALFGBG-715986) from the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement.
Funding Information:
HH is an employee of Eisai Inc. This work has been performed during his previous position at Sorbonne University, Paris, France. At Sorbonne University, he was supported by the AXA Research Fund, the “Fondation partenariale Sorbonne Université”, and the “Fondation pour la Recherche sur Alzheimer”, Paris, France.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - Biomarkers
KW - Mild cognitive impairment
KW - Neurofilament light chain
KW - Subjective memory complainers
KW - Tau
UR - http://www.scopus.com/inward/record.url?scp=85095951390&partnerID=8YFLogxK
U2 - 10.1186/s13195-020-00704-4
DO - 10.1186/s13195-020-00704-4
M3 - Article
C2 - 33183357
AN - SCOPUS:85095951390
SN - 1758-9193
VL - 12
JO - Alzheimer's Research and Therapy
JF - Alzheimer's Research and Therapy
IS - 1
M1 - 147
ER -