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

Filippo Baldacci, Simone Lista, Maria Laura Manca, Patrizia A Chiesa, Enrica Cavedo, Pablo Lemercier, Henrik Zetterberg, Kaj Blennow, Marie-Odile Habert, Marie Claude Potier, Bruno Dubois, Andrea Vergallo, Harald Hampel

Journal: Alzheimer's research & therapy 2021;12(1):147

PMID: 33183357

Free Full Text on BioMed Central View on PubMed

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.

Address: Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, F-75013, Paris, France. [email protected].; Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56125, Pisa, Italy. [email protected].; 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.; Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56125, Pisa, Italy.; Department of Mathematics, University of Pisa, Pisa, Italy.; 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.; 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.; 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.; 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.; 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.; Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, F-75013, Paris, France.

DOI: 10.1186/s13195-020-00704-4

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MeSH Terms: Alzheimer Disease, Amyloid beta-Peptides, Biomarkers, Cognitive Dysfunction, Female, Follow-Up Studies, Humans, Male, Neurofilament Proteins, tau Proteins