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Longitudinal stability of cerebrospinal fluid biomarker levels: fulfilled requirement for pharmacodynamic markers in Alzheimer's disease.
J Alzheimers Dis 2013; 33(3):807-22JA

Abstract

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-β(1-42) (Aβ(1-42)), total tau protein (T-tau), and hyperphosphorylated tau (P-tau(181P)), 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 Aβ(1-42), T-tau, and P-tau(181P) 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 Aβ(1-42) and P-tau(181P) 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 Aβ(1-42), T-tau, and P-tau(181P) 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+Show Affiliations

Laboratory of Neurochemistry and Behavior, Reference Center for Biological Markers of Dementia (BIODEM), Antwerp, Belgium. nathalie.lebastard@ua.ac.be

Pub Type(s)

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

Language

eng

PubMed ID

23034521

Citation

Le Bastard, Nathalie, et al. "Longitudinal Stability of Cerebrospinal Fluid Biomarker Levels: Fulfilled Requirement for Pharmacodynamic Markers in Alzheimer's Disease." Journal of Alzheimer's Disease : JAD, vol. 33, no. 3, 2013, pp. 807-22.
Le Bastard N, Aerts L, Sleegers K, et al. Longitudinal stability of cerebrospinal fluid biomarker levels: fulfilled requirement for pharmacodynamic markers in Alzheimer's disease. J Alzheimers Dis. 2013;33(3):807-22.
Le Bastard, N., Aerts, L., Sleegers, K., Martin, J. J., Van Broeckhoven, C., De Deyn, P. P., & Engelborghs, S. (2013). Longitudinal stability of cerebrospinal fluid biomarker levels: fulfilled requirement for pharmacodynamic markers in Alzheimer's disease. Journal of Alzheimer's Disease : JAD, 33(3), pp. 807-22. doi:10.3233/JAD-2012-110029.
Le Bastard N, et al. Longitudinal Stability of Cerebrospinal Fluid Biomarker Levels: Fulfilled Requirement for Pharmacodynamic Markers in Alzheimer's Disease. J Alzheimers Dis. 2013;33(3):807-22. PubMed PMID: 23034521.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Longitudinal stability of cerebrospinal fluid biomarker levels: fulfilled requirement for pharmacodynamic markers in Alzheimer's disease. AU - Le Bastard,Nathalie, AU - Aerts,Laetitia, AU - Sleegers,Kristel, AU - Martin,Jean-Jacques, AU - Van Broeckhoven,Christine, AU - De Deyn,Peter Paul, AU - Engelborghs,Sebastiaan, PY - 2012/10/5/entrez PY - 2012/10/5/pubmed PY - 2013/6/26/medline SP - 807 EP - 22 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 33 IS - 3 N2 - 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-β(1-42) (Aβ(1-42)), total tau protein (T-tau), and hyperphosphorylated tau (P-tau(181P)), 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 Aβ(1-42), T-tau, and P-tau(181P) 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 Aβ(1-42) and P-tau(181P) 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 Aβ(1-42), T-tau, and P-tau(181P) 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. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/23034521/Longitudinal_stability_of_cerebrospinal_fluid_biomarker_levels:_fulfilled_requirement_for_pharmacodynamic_markers_in_Alzheimer's_disease_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-2012-110029 DB - PRIME DP - Unbound Medicine ER -