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A more recent version of this article appeared on December 1, 2005.
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M500207-MCP200v1
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Submitted on July 11, 2005
Revised on September 30, 2005
Accepted on September 30, 2005

Comparative proteomics analysis of intra- and inter-individual variation in human cerebrospinal fluid

Yan Hu, James P. Malone, Anne M. Fagan, R. Reid Townsend, and David M. Holtzman

Neurology Dept., Washington University, St. Louis, MO 63110

Corresponding Author: holtzman{at}neuro.wustl.edu

Cerebrospinal fluid (CSF) is a potential source of biomarkers for many disorders of the central nervous system (CNS), including Alzheimer’s disease (AD). Prior to comparing CSF samples between individuals to identify patterns of disease-associated proteins, it is important to examine variation within individuals over a short period of time so that one can better interpret potential changes in CSF between individuals, as well as changes within a given individual over a longer time span. In this study, we analyzed 12 CSF samples, composed of pairs of samples from 6 individuals, obtained 2 weeks apart. Multi-affinity depletion, 2-D DIGE and tandem mass spectrometry were employed. A number of proteins whose abundance varied between the two time points were identified for each individual. Some of these proteins were commonly identified in multiple individuals. More importantly, despite the intra-individual variations, hierarchical clustering and multidimensional-scaling analysis of the proteomic profiles revealed that two CSF samples from the same individual cluster the closest together, and the between-subject variability is much larger than the within-subject variability. Among the 6 subjects, comparison between the 4 cognitively normal and the 2 very mildly demented subjects also yielded some proteins that have been identified in previous AD biomarker studies. These results validate our method of identifying differences in proteomic profiles of CSF samples and have important implications for the design of CSF biomarker studies for AD and other CNS disorders.


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