Longitudinal stability of CSF biomarkers in Alzheimer's disease
2007 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 419, no 1, 18-22 p.Article in journal (Refereed) Published
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-tau181) and the 42 amino acid isoform of β-amyloid (Aβ42), 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 Aβ42 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, Aβ immunotherapy and tau phosphorylation inhibitors.
Place, publisher, year, edition, pages
2007. Vol. 419, no 1, 18-22 p.
Biomarkers, β-Amyloid, Cerebrospinal fluid (CSF), Clinical trials, Longitudinal, Tau protein
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-11010DOI: 10.1016/j.neulet.2007.03.064ISI: 000246815200005PubMedID: 17482358OAI: oai:DiVA.org:uu-11010DiVA: diva2:38778