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.
The present study examines the extent of spinal cerebrospinal fluid (CSF) absorption in healthy individuals in relation to physical activity, CSF production, intracranial pressure (ICP), and spinal CSF movement. Thirty-four healthy individuals aged 21-35 yr were examined by lumbar puncture and radionuclide cisternography with repeated imaging. ICP was registered before and after CSF drainage, and CSF production was calculated. Spinal CSF absorption was calculated as reduction in spinal radionuclide activity. The radionuclide activity in the spinal subarachnoidal space was gradually decreased by 20 Ϯ 13% (mean Ϯ SD) during 1 h. The reduction was higher in active than in resting individuals (27 Ϯ 12% vs. 13 Ϯ 9%). The mean ICP in 19 of the individuals was 13.6 Ϯ 3.1 cmH 2O. B-waves were found in 79% of the individuals, with a mean frequency of 0.6 Ϯ 0.3 min Ϫ1 . The mean CSF production rate was 0.34 Ϯ 0.13 ml/min. There were no correlations between radionuclide reduction, spinal movement of the radionuclide, and CSF production rate. The spinal radionuclide reduction found in this study indicates a spinal CSF absorption of 0.11-0.23 ml/min, more pronounced in active than in resting individuals. arachnoid villi; cerebrospinal fluid spinal flow; cerebrospinal fluid production; cerebrospinal fluid pressure; radionuclide imaging CEREBROSPINAL FLUID (CSF) is mainly produced in the choroid plexus in the lateral, third, and fourth ventricles, and a minor part is derived from the extracellular space of the brain (37). The CSF flows in a to-and-fro movement with a caudaldirected net flow through the aqueduct of Sylvius and foramina of Luschka and Magendie into the spinal subarachnoidal space (SAS) (39). The pulsative brain movements create a "mixing" of CSF in the fourth ventricle, basal cisterns, and upper spinal SAS (17, 23). Older radionuclide cisternographic (RC) studies have shown that radioactively labeled substances move upward when injected in the lumbar region (11) and downward when injected in the ventricles (12). Within the spinal SAS, a pulsatile to-and-fro flow with a caudal-directed net flow in the ventral and a cranial-directed net flow in the lateral cervical SAS has been reported (25, 42). However, the existence of a CSF bulk flow in any direction within the spinal SAS has been questioned, and RC and MRI observations could be explained by mere diffusion (22). The arachnoid villi in the superior sagittal sinus have generally been thought to be the main site for CSF absorption in humans (2, 40). However, lymphatic drainage pathways have been shown in animal studies to play an important role for CSF clearance (5,27,46). The existence of this pathway in humans remains unclear. Spinal CSF absorption through arachnoid granulations located along the nerve roots, morphologically similar to cranial villi, was suggested by Kido et al. (28), and CSF clearance from the spinal SAS has been demonstrated in sheep and cats (6, 31). The extent and importance of the spinal absorption pathway in humans remain unclear and, to ...
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