Age-Dependency of Total Tau in the Cerebrospinal Fluid Is Corrected by Amyloid-β 1–40: A Correlational Study in Healthy Adults

Article type: Research Article

Authors: Zebhauser, Paul Theo^{a; b; *} | Berthele, Achim^a | Franz, Marie-Sophie^c | Goldhardt, Oliver^b | Diehl-Schmid, Janine^b | Priller, Josef^{b; d; e} | Ortner, Marion^{b; 1} | Grimmer, Timo^{b; 1}

Affiliations: [a] Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany | [b] Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany | [c] Department of Anesthesiology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany | [d] Charité-Universitätsmedizin Berlin and DZNE, Berlin, Germany | [e] University of Edinburgh and UK Dementia Research Institute, Edinburgh, UK

Correspondence: [*] Correspondence to: Paul Theo Zebhauser, Department of Neurology, Klinikum rechts der Isar, Ismaninger Straße 22, 81675 Munich, Germany. Tel.: +49 089 4140 5938; E-mail: paul.zebhauser@tum.de.

Note: [1] These authors contributed equally to this work.

Abstract: Background:Tau proteins are established biomarkers of neuroaxonal damage in a wide range of neurodegenerative conditions. Although measurement of total-Tau in the cerebrospinal fluid is widely used in research and clinical settings, the relationship between age and total-Tau in the cerebrospinal fluid is yet to be fully understood. While past studies reported a correlation between age and total-Tau in the cerebrospinal fluid of healthy adults, in clinical practice the same cut-off value is used independently of patient’s age. Objective:To further explore the relationship between age and total-Tau and to disentangle neurodegenerative from drainage-dependent effects. Methods:We analyzed cerebrospinal fluid samples of 76 carefully selected cognitively healthy adults and included amyloid-β 1–40 as a potential marker of drainage from the brain’s interstitial system. Results:We found a significant correlation of total-Tau and age, which was no longer present when correcting total-Tau for amyloid-β 1–40 concentrations. These findings were replicated under varied inclusion criteria. Conclusion:Results call into question the association of age and total-Tau in the cerebrospinal fluid. Furthermore, they suggest diagnostic utility of amyloid-β 1–40 as a possible proxy for drainage-mechanisms into the cerebrospinal fluid when interpreting biomarker concentrations for neurodegenerative diseases.

Keywords: Alzheimer’s disease, amyloid-beta 1–40, tau proteins, total-Tau

DOI: 10.3233/JAD-210286

Journal: Journal of Alzheimer's Disease, vol. 83, no. 1, pp. 155-162, 2021