Document Detail


Longitudinal Stability of Cerebrospinal Fluid Biomarker Levels: Fulfilled Requirement for Pharmacodynamic Markers in Alzheimer's Disease.
MedLine Citation:
PMID:  23034521     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The current treatment for Alzheimer's disease (AD) is purely symptomatic, but medications interfering with underlying pathophysiological processes are being developed. To evaluate a possible disease-modifying effect, cerebrospinal fluid (CSF) biomarkers with a direct link to the underlying pathophysiology, such as amyloid-β1-42 (Aβ1-42), total tau protein (T-tau), and hyperphosphorylated tau (P-tau181P), may play an important role. If intra-individual fluctuations in biomarker levels are small, the difference between two samples could serve as a pharmacodynamic measure. The aim of this study was to evaluate the longitudinal stability of CSF Aβ1-42, T-tau, and P-tau181P levels in AD patients and control subjects. Serial CSF samples of 28 AD patients and 23 controls with a minimum time interval of 30 days were included in this study. Serial CSF samples from 10 progressive patients (7 mild cognitive impairment (MCI) patients and 3 controls progressing to MCI or AD) were also analyzed. Intra-individual CSF Aβ1-42 and P-tau181P levels were stable in AD and controls. Intra-individual CSF T-tau levels differed significantly in AD patients, but not in controls. Change in biomarker concentrations per time unit was also significant between groups, but not within groups. The difference in biomarker levels in samples from progressive patients was not significant. In conclusion, CSF levels of Aβ1-42, T-tau, and P-tau181P are relatively stable over time. Only T-tau increased in AD patients in comparison to controls, which does not preclude its use as a diagnostic marker, nor as a potential pharmacodynamic marker.
Authors:
Nathalie Le Bastard; Laetitia Aerts; Kristel Sleegers; Jean-Jacques Martin; Christine Van Broeckhoven; Peter Paul De Deyn; Sebastiaan Engelborghs
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-3
Journal Detail:
Title:  Journal of Alzheimer's disease : JAD     Volume:  -     ISSN:  1875-8908     ISO Abbreviation:  J. Alzheimers Dis.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9814863     Medline TA:  J Alzheimers Dis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratory of Neurochemistry and Behavior, Reference Center for Biological Markers of Dementia (BIODEM), Antwerp, Belgium.
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