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Longitudinal Stability Evaluation of Biomarkers and Their Correlation in Cerebrospinal Fluid and Plasma from Patients with Alzheimer's Disease
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2012 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 32, no 4, 939-947 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
Alzheimer's disease, biomarkers, cerebrospinal fluid, longitudinal, plasma, stability
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-189933DOI: 10.3233/JAD-2012-120976ISI: 000311227200007PubMedID: 22936008OAI: oai:DiVA.org:uu-189933DiVA: diva2:582575
Available from: 2013-01-04 Created: 2013-01-04 Last updated: 2017-12-06Bibliographically approved

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Basun, HansLannfelt, Lars

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