Tau and Aβ42 in Cerebrospinal Fluid from Healthy Adults 21–93 Years of Age: Establishment of Reference Values

Abstract

Abstract Background: Tau protein and the 42-amino acid form of β-amyloid (Aβ42) measured in cerebrospinal fluid (CSF) have been proposed as potential biochemical diagnostic markers for Alzheimer disease. For the introduction of these assays in clinical practice, adequate reference values are of importance. Methods: CSF samples were obtained from 231 neurologically and psychiatrically healthy individuals, 21–93 years of age, all with a MiniMental State examination score of 28 or above. Standardized ELISAs were used to measure tau and Aβ42 in CSF. Following IFCC recommendations, we used a rank-based method; the 0.90 and 0.10 fractiles were estimated to establish reference values for CSF-tau and CSF-Aβ42, respectively. Putative confounding factors, such as the influence of the passage of proteins from peripheral blood to CSF, influence of dysfunction of the blood-brain barrier, and freezing and thawing of CSF, were investigated. Results: A correlation with age was found for CSF-tau (r = 0.60; P <0.001). Therefore, separate reference values for different age groups were established for CSF-tau: <300 ng/L in the group 21–50 years of age, <450 ng/L in the group 51–70 years of age, and <500 ng/L in the group 71–93 years of age. CSF-Aβ42 did not correlate with age (r = −0.045), and the reference value was set to >500 ng/L. No correlation was found between blood-brain barrier function and CSF-tau or CSF-Aβ42. Conclusions: These reference values can be applied when using CSF-tau and CSF-Aβ42 in clinical practice.