Longitudinal Stability Evaluation of Biomarkers and Their Correlation in Cerebrospinal Fluid and Plasma from Patients with Alzheimer's Disease
2012 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, Vol. 32, no 4, 939-947 p.Article in journal (Refereed) Published
There is an increasing demand for biomarkers in clinical treatment trials to demonstrate target engagement and to support disease modification claims. To be able to detect treatment related effects, a prerequisite is that the levels of the biomarker are stable over time or that the change over time is known. In the present study, the stability of alpha- and beta-cleaved soluble amyloid-beta protein precursor (sA beta PP alpha and sA beta PP beta), A beta(1-40) together with the phosphorylated form of neurofilament heavy/medium (pNfH/M) in cerebrospinal fluid (CSF) was analyzed in a cohort of 51 patients with Alzheimer's disease. In addition, the stability of A beta(1-40), beta(1-42), and sA beta PP beta in plasma was explored. Plasma and CSF was sampled at baseline and after 6-months follow up, and all patients were on stable treatment with acetylcholinesterase inhibitors. During this 6-month longitudinal follow-up, we saw a small, but consistent and statistically significant increase in CSF levels of sA beta PP beta (103% of baseline levels) and a statistically significant decrease in the CSF levels of pNfH/M (91% of baseline levels). The mean level of the CSF biomarkers were very stable between baseline and endpoint, with within-patients coefficients of variation (CVs) of 5.84-17.3%, while the variability was larger for the plasma biomarkers, with CVs of 14.1-42.3%. This stability suggests that these biomarkers may have the potential to detect and monitor biochemical changes induced by disease-modifying drugs.
Place, publisher, year, edition, pages
2012. Vol. 32, no 4, 939-947 p.
Alzheimer's disease, biomarkers, cerebrospinal fluid, longitudinal, plasma, stability
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-189933DOI: 10.3233/JAD-2012-120976ISI: 000311227200007PubMedID: 22936008OAI: oai:DiVA.org:uu-189933DiVA: diva2:582575