Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Nov 12;12(1):147.
doi: 10.1186/s13195-020-00704-4.

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

Filippo Baldacci  1   2 , Simone Lista  3   4   5 , Maria Laura Manca  6   7 , Patrizia A Chiesa  3   4   5 , Enrica Cavedo  3   4   5   8 , Pablo Lemercier  3   4   5 , Henrik Zetterberg  9   10   11   12 , Kaj Blennow  9   10 , Marie-Odile Habert  13   14   15 , Marie Claude Potier  16 , Bruno Dubois  3   4   5 , Andrea Vergallo  3 , Harald Hampel  3 ; INSIGHT-preAD study group; Alzheimer Precision Medicine Initiative (APMI)
Collaborators, Affiliations

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

Filippo Baldacci et al. Alzheimers Res Ther. .

Abstract

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.

Keywords: Alzheimer’s disease; Biomarkers; Mild cognitive impairment; Neurofilament light chain; Subjective memory complainers; Tau.

PubMed Disclaimer

Conflict of interest statement

SL received lecture honoraria from Roche and Servier.

AV is an employee of Eisai Inc. He does not receive any fees or honoraria since November 2019. Before November 2019 he had received lecture honoraria from Roche, MagQu LLC, and Servier.

HH is an employee of Eisai Inc. and serves as Senior Associate Editor for the Journal Alzheimer’s & Dementia and does not receive any fees or honoraria since May 2019; before May 2019, he had received lecture fees from Servier, Biogen and Roche; research grants from Pfizer, Avid, and MSD Avenir (paid to the institution); travel funding from Functional Neuromodulation, Axovant, Eli Lilly and company, Takeda and Zinfandel, GE-Healthcare and Oryzon Genomics; consultancy fees from Qynapse, Jung Diagnostics, Cytox Ltd., Axovant, Anavex, Takeda and Zinfandel, GE Healthcare and Oryzon Genomics, and Functional Neuromodulation; and participated in scientific advisory boards of Functional Neuromodulation, Axovant, Eisai, Eli Lilly and company, Cytox Ltd., GE Healthcare, Takeda and Zinfandel, Oryzon Genomics and Roche Diagnostics.

He is co-inventor in the following patents as a scientific expert and has received no royalties:

• In Vitro Multiparameter Determination Method for The Diagnosis and Early Diagnosis of Neurodegenerative Disorders Patent Number: 8916388.

• In Vitro Procedure for Diagnosis and Early Diagnosis of Neurodegenerative Diseases Patent Number: 8298784.

• Neurodegenerative Markers for Psychiatric Conditions Publication Number: 20120196300.

• In Vitro Multiparameter Determination Method for The Diagnosis and Early Diagnosis of Neurodegenerative Disorders Publication Number: 20100062463.

• In Vitro Method for The Diagnosis and Early Diagnosis of Neurodegenerative Disorders Publication Number: 20100035286.

• In Vitro Procedure for Diagnosis and Early Diagnosis of Neurodegenerative Diseases Publication Number: 20090263822.

• In Vitro Method for The Diagnosis of Neurodegenerative Diseases Patent Number: 7547553.

• CSF Diagnostic in Vitro Method for Diagnosis of Dementias and Neuroinflammatory Diseases Publication Number: 20080206797.

• In Vitro Method for The Diagnosis of Neurodegenerative Diseases Publication Number: 20080199966.

• Neurodegenerative Markers for Psychiatric Conditions Publication Number: 20080131921.

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.

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.

Figures

Fig. 1
Fig. 1
Plasma NFL changes overtime. The first graph (a) showed repeated measurements at baseline (T0), 1-year follow-up (T1), and 3-year follow-up (T2). The second one (b) charted differences for plasma NFL concentrations stratified by sex at the three time points. The third graph (c) reported within person plasma NFL trajectories. Data are referred to a subset of SMC (N = 79) who performed T0, T1, and T2 blood samples. Abbreviations: F, female; M, male; NFL, neurofilament light chain; SMC, subjective memory complainers; t-Tau, total Tau; T0, baseline; T1, 1-year follow-up; T2, 3-year follow-up
Fig. 2
Fig. 2
Plasma t-Tau changes overtime. The first graph (a) showed repeated measurements at baseline (T0), 1-year follow-up (T1), and 3-year follow-up (T2). The second one (b) charted differences for plasma t-Tau concentrations stratified by sex at the three time points. The third graph (c) reported within person plasma t-Tau trajectories. Data are referred to a subset of SMC (N = 79) who performed T0, T1, and T2 blood samples. Abbreviations: F, female; M, male; NFL, neurofilament light chain; SMC, subjective memory complainers; t-Tau, total Tau; T0, baseline; T1, 1-year follow-up; T2, 3-year follow-up
See this image and copyright information in PMC

References

    1. Molinuevo JL, Ayton S, Batrla R, Bednar MM, Bittner T, Cummings J, et al. Current state of Alzheimer’s fluid biomarkers. Acta Neuropathol (Berl) 2018;136:821–853. doi: 10.1007/s00401-018-1932-x. - DOI - PMC - PubMed
    1. Mattsson N, Zetterberg H, Janelidze S, Insel PS, Andreasson U, Stomrud E, et al. Plasma tau in Alzheimer disease. Neurology. 2016;87:1827–1835. doi: 10.1212/WNL.0000000000003246. - DOI - PMC - PubMed
    1. Mattsson N, Andreasson U, Zetterberg H, Blennow K. Alzheimer’s disease neuroimaging initiative. Association of plasma neurofilament light with neurodegeneration in patients with Alzheimer disease. JAMA Neurol. 2017;74:557–566. doi: 10.1001/jamaneurol.2016.6117. - DOI - PMC - PubMed
    1. Hampel H, O’Bryant SE, Molinuevo JL, Zetterberg H, Masters CL, Lista S, et al. Blood-based biomarkers for Alzheimer disease: mapping the road to the clinic. Nat Rev Neurol. 2018. 10.1038/s41582-018-0079-7. - PMC - PubMed
    1. Khalil M, Teunissen CE, Otto M, Piehl F, Sormani MP, Gattringer T, et al. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol. 2018;14:577–589. doi: 10.1038/s41582-018-0058-z. - DOI - PubMed

Publication types