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

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.