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Longitudinal stability of CSF biomarkers in Alzheimer's disease.
Neurosci Lett 2007; 419(1):18-22NL

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 (Abeta42), 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 Abeta42 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, Abeta immunotherapy and tau phosphorylation inhibitors.

Authors+Show Affiliations

Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. kaj.blennow@neuro.gu.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17482358

Citation

Blennow, Kaj, et al. "Longitudinal Stability of CSF Biomarkers in Alzheimer's Disease." Neuroscience Letters, vol. 419, no. 1, 2007, pp. 18-22.
Blennow K, Zetterberg H, Minthon L, et al. Longitudinal stability of CSF biomarkers in Alzheimer's disease. Neurosci Lett. 2007;419(1):18-22.
Blennow, K., Zetterberg, H., Minthon, L., Lannfelt, L., Strid, S., Annas, P., ... Andreasen, N. (2007). Longitudinal stability of CSF biomarkers in Alzheimer's disease. Neuroscience Letters, 419(1), pp. 18-22.
Blennow K, et al. Longitudinal Stability of CSF Biomarkers in Alzheimer's Disease. Neurosci Lett. 2007 May 23;419(1):18-22. PubMed PMID: 17482358.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2007/04/06/ PY - 2007/02/26/received PY - 2007/03/15/revised PY - 2007/03/16/accepted PY - 2007/5/8/pubmed PY - 2007/7/25/medline PY - 2007/5/8/entrez SP - 18 EP - 22 JF - Neuroscience letters JO - Neurosci. Lett. VL - 419 IS - 1 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 (Abeta42), 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 Abeta42 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, Abeta immunotherapy and tau phosphorylation inhibitors. SN - 0304-3940 UR - https://www.unboundmedicine.com/medline/citation/17482358/Longitudinal_stability_of_CSF_biomarkers_in_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(07)00342-4 DB - PRIME DP - Unbound Medicine ER -