Longitudinal stability of CSF biomarkers in Alzheimer's disease

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Longitudinal stability of CSF biomarkers in Alzheimer's disease. / Blennow, Kaj; Zetterberg, Henrik; Minthon, Lennart; Lannfelt, Lars; Strid, Stig; Annas, Peter; Basun, Hans; Andreasen, Niels.

In: Neuroscience Letters, Vol. 419, No. 1, 2007, p. 18-22.

Research output: Contribution to journalArticle

Harvard

Blennow, K, Zetterberg, H, Minthon, L, Lannfelt, L, Strid, S, Annas, P, Basun, H & Andreasen, N 2007, 'Longitudinal stability of CSF biomarkers in Alzheimer's disease', Neuroscience Letters, vol. 419, no. 1, pp. 18-22. https://doi.org/10.1016/j.neulet.2007.03.064

APA

Blennow, K., Zetterberg, H., Minthon, L., Lannfelt, L., Strid, S., Annas, P., Basun, H., & Andreasen, N. (2007). Longitudinal stability of CSF biomarkers in Alzheimer's disease. Neuroscience Letters, 419(1), 18-22. https://doi.org/10.1016/j.neulet.2007.03.064

CBE

Blennow K, Zetterberg H, Minthon L, Lannfelt L, Strid S, Annas P, Basun H, Andreasen N. 2007. Longitudinal stability of CSF biomarkers in Alzheimer's disease. Neuroscience Letters. 419(1):18-22. https://doi.org/10.1016/j.neulet.2007.03.064

MLA

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Author

Blennow, Kaj ; Zetterberg, Henrik ; Minthon, Lennart ; Lannfelt, Lars ; Strid, Stig ; Annas, Peter ; Basun, Hans ; Andreasen, Niels. / Longitudinal stability of CSF biomarkers in Alzheimer's disease. In: Neuroscience Letters. 2007 ; Vol. 419, No. 1. pp. 18-22.

RIS

TY - JOUR

T1 - Longitudinal stability of CSF biomarkers in Alzheimer's disease

AU - Blennow, Kaj

AU - Zetterberg, Henrik

AU - Minthon, Lennart

AU - Lannfelt, Lars

AU - Strid, Stig

AU - Annas, Peter

AU - Basun, Hans

AU - Andreasen, Niels

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

KW - clinical trials

KW - cerebrospinal fluid (CSF)

KW - biomarkers

KW - beta-amyloid

KW - tau protein

KW - longitudinal

U2 - 10.1016/j.neulet.2007.03.064

DO - 10.1016/j.neulet.2007.03.064

M3 - Article

C2 - 17482358

VL - 419

SP - 18

EP - 22

JO - Neuroscience Letters

JF - Neuroscience Letters

SN - 0304-3940

IS - 1

ER -