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Longitudinal stability of CSF biomarkers in Alzheimer's disease

Blennow, Kaj; Zetterberg, Henrik; Minthon, Lennart LU ; Lannfelt, Lars; Strid, Stig; Annas, Peter; Basun, Hans and Andreasen, Niels (2007) In Neuroscience Letters 419(1). p.18-22
Abstract
Biomarker levels in cerebrospinal fluid (CSF) may serve as surrogate markers for treatment efficacy in clinical trials of disease-modifying drugs against Alzheimer's disease (AD). A prerequisite, however, is that the marker is sufficiently stable over time in individual patients. Here, we tested the stability of the three established CSF biomarkers for AD, total tau (T-tau), tau phosphorylated at threonine 181 (P-tau(181)) and the 42 amino acid isoform of beta-amyloid (A beta 42), over 6 months in a cohort of AD patients on stable treatment with acetylcholinesterase (AChE) inhibitors. Fifty-three patients completed the study, 29 men and 24 women, mean age (+/- S.D.) 76.1 +/- 7.9 years. Mean levels of CSF biomarkers were very stable between... (More)
Biomarker levels in cerebrospinal fluid (CSF) may serve as surrogate markers for treatment efficacy in clinical trials of disease-modifying drugs against Alzheimer's disease (AD). A prerequisite, however, is that the marker is sufficiently stable over time in individual patients. Here, we tested the stability of the three established CSF biomarkers for AD, total tau (T-tau), tau phosphorylated at threonine 181 (P-tau(181)) and the 42 amino acid isoform of beta-amyloid (A beta 42), over 6 months in a cohort of AD patients on stable treatment with acetylcholinesterase (AChE) inhibitors. Fifty-three patients completed the study, 29 men and 24 women, mean age (+/- S.D.) 76.1 +/- 7.9 years. Mean levels of CSF biomarkers were very stable between baseline and endpoint, with coefficients of variation (CVs) of 4.4-6.1%. Intra-individual biomarker levels at baseline and endpoint were also highly correlated with Pearson r-values above 0.95 (p < 0.0001), for all three markers. We conclude that T-tau, P-tau and A beta 42 concentrations in CSF are remarkably stable over a 6-month period in individual AD patients. This suggest that these biomarkers may have a potential to identify and monitor very minor biochemical changes induced by treatment, and thus support their possible usefulness as surrogate markers in clinical trials with drug candidates with disease-modifying potential, such as secretase inhibitors, A beta immunotherapy and tau phosphorylation inhibitors. (c) 2007 Elsevier Ireland Ltd. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
clinical trials, cerebrospinal fluid (CSF), biomarkers, beta-amyloid, tau protein, longitudinal
in
Neuroscience Letters
volume
419
issue
1
pages
18 - 22
publisher
Elsevier
external identifiers
  • wos:000246815200005
  • scopus:34247893817
ISSN
0304-3940
DOI
10.1016/j.neulet.2007.03.064
language
English
LU publication?
yes
id
6a2db2e6-83c8-41a9-8f0c-82a25cbb41cd (old id 657427)
date added to LUP
2007-12-10 14:47:32
date last changed
2017-10-22 03:56:24
@article{6a2db2e6-83c8-41a9-8f0c-82a25cbb41cd,
  abstract     = {Biomarker levels in cerebrospinal fluid (CSF) may serve as surrogate markers for treatment efficacy in clinical trials of disease-modifying drugs against Alzheimer's disease (AD). A prerequisite, however, is that the marker is sufficiently stable over time in individual patients. Here, we tested the stability of the three established CSF biomarkers for AD, total tau (T-tau), tau phosphorylated at threonine 181 (P-tau(181)) and the 42 amino acid isoform of beta-amyloid (A beta 42), over 6 months in a cohort of AD patients on stable treatment with acetylcholinesterase (AChE) inhibitors. Fifty-three patients completed the study, 29 men and 24 women, mean age (+/- S.D.) 76.1 +/- 7.9 years. Mean levels of CSF biomarkers were very stable between baseline and endpoint, with coefficients of variation (CVs) of 4.4-6.1%. Intra-individual biomarker levels at baseline and endpoint were also highly correlated with Pearson r-values above 0.95 (p &lt; 0.0001), for all three markers. We conclude that T-tau, P-tau and A beta 42 concentrations in CSF are remarkably stable over a 6-month period in individual AD patients. This suggest that these biomarkers may have a potential to identify and monitor very minor biochemical changes induced by treatment, and thus support their possible usefulness as surrogate markers in clinical trials with drug candidates with disease-modifying potential, such as secretase inhibitors, A beta immunotherapy and tau phosphorylation inhibitors. (c) 2007 Elsevier Ireland Ltd. All rights reserved.},
  author       = {Blennow, Kaj and Zetterberg, Henrik and Minthon, Lennart and Lannfelt, Lars and Strid, Stig and Annas, Peter and Basun, Hans and Andreasen, Niels},
  issn         = {0304-3940},
  keyword      = {clinical trials,cerebrospinal fluid (CSF),biomarkers,beta-amyloid,tau protein,longitudinal},
  language     = {eng},
  number       = {1},
  pages        = {18--22},
  publisher    = {Elsevier},
  series       = {Neuroscience Letters},
  title        = {Longitudinal stability of CSF biomarkers in Alzheimer's disease},
  url          = {http://dx.doi.org/10.1016/j.neulet.2007.03.064},
  volume       = {419},
  year         = {2007},
}