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

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.

Zn(II)‐ and Cu(II)‐induced non‐fibrillar aggregates of amyloid‐β (1–42) peptide are transformed to amyloid fibrils, both spontaneously and under the influence of metal chelators

“…The removal of Zn(II) induced Ab fibrillization in our experiments. However, at low physiological Ab concentrations 0.11 nmol/L in brain (Sjogren et al 2001) the fibrillization of monomeric Ab is a slow and unlikely process. It is repeatedly demonstrated that introduction of Ab 42 into brain cannot induce amyloid formation in vivo (Meyer-Luehmann et al 2006).…”

Cerebrospinal fluid tau protein is not a biological marker in amyotrophic lateral sclerosis

“…The increased CSF tau in the bulbar-onset patients is explained by the higher mean age of this specific group. It has been shown in fact that there is an increase of CSF tau in normal aging which may reflect a physiological mild progressive neuronal degeneration [12]. Furthermore, we took all precautions in order to reduce the risk of an artifactual change of the CSF tau level, such as the use of polypropylene tubes, storage of CSF samples at)80°C, and avoiding freezing-thawing procedures [12].…”

“…It has been shown in fact that there is an increase of CSF tau in normal aging which may reflect a physiological mild progressive neuronal degeneration [12]. Furthermore, we took all precautions in order to reduce the risk of an artifactual change of the CSF tau level, such as the use of polypropylene tubes, storage of CSF samples at)80°C, and avoiding freezing-thawing procedures [12]. In addition, we did not analyze in this study of CSF samples (either from ALS cases or controls) a measured total protein falling outside the higher normal cut-off level given by our laboratory (i.e.…”

“…Even for the phosphorylated tau, data are in some way conflicting. Whilst Strong et al, 2006 [11] described a tau protein hyperphosphorylation in the frontal cortex of cognitively-impaired sporadic ALS, no changes of the phosphorylated tau could be demonstrated in the CSF of ALS patients and controls [12].…”

Neuropathology of prodromal Lewy body disease

“…16 Cerebrospinal fluid levels of total s, phosphorylated s, and amyloid-b were normal. 17 Neurological examination was normal. DAT imaging showed decreased uptake in the right and left putamen ( Fig.…”