Longitudinal stability of CSF biomarkers in Alzheimer's disease

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title = "Longitudinal stability of CSF biomarkers in Alzheimer's disease",
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 < 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.",
keywords = "clinical trials, cerebrospinal fluid (CSF), biomarkers, beta-amyloid, tau protein, longitudinal",
author = "Kaj Blennow and Henrik Zetterberg and Lennart Minthon and Lars Lannfelt and Stig Strid and Peter Annas and Hans Basun and Niels Andreasen",
year = "2007",
doi = "10.1016/j.neulet.2007.03.064",
language = "English",
volume = "419",
pages = "18--22",
journal = "Neuroscience Letters",
issn = "0304-3940",
publisher = "Elsevier",
number = "1",