Tau and Abeta42 in cerebrospinal fluid from healthy adults 21-93 years of age: establishment of reference values.
BACKGROUND
Tau protein and the 42-amino acid form of beta-amyloid (Abeta42) 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 Abeta42 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-Abeta42, 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-Abeta42 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-Abeta42.


CONCLUSIONS
These reference values can be applied when using CSF-tau and CSF-Abeta42 in clinical practice.
Sjögren
M
M
Institute of Clinical Neuroscience, Psychiatry Section, Göteborg University, SE 431 80 Mölndal, Sweden. magnus.sjogren@medfak.gu.se
Vanderstichele
H
H
Agren
H
H
Zachrisson
O
O
Edsbagge
M
M
Wikkelsø
C
C
Skoog
I
I
Wallin
A
A
Wahlund
L O
LO
Marcusson
J
J
Nägga
K
K
Andreasen
N
N
Davidsson
P
P
Vanmechelen
E
E
Blennow
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D012016:Reference Values
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)