. Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins. Nat Med. 2007 Nov;13(11):1359-62. PubMed.

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  1. Are Blood Samples Being Archived for Optimal Subsequent Utility?
    Anne Fagan, John Trojanowski, and Eric Blalock have commented on the excellence and the caveats of the study by Ray et al. Rather than expound on what my colleagues have already covered well, I would like to pick up on one comment by Tony Wyss-Coray that is crucial for studies of blood biomarkers. He is quoted as having said “many clinics do not collect blood for plasma, but instead freeze it or use it for serum.” He said that “plasma must be immediately prepared from the serum and then frozen.”

    This comment addresses a major issue with the collection and processing of blood samples for archiving and further study. Consider the major components of blood as serum, buffy coat, and erythrocytes. Wyss-Coray has commented on the fact that many clinics do not treat serum in a way that is appropriate for plasma, and he suggests a procedure that would be compatible with his method. Similarly, we have found that both protein and message extracted from cells contained in frozen buffy coat samples archived at several centers are badly degraded to the point of being useless. We have developed methods for collecting and processing leukocytes that preserve their utility for studies of gene expression (Mhyre et al., in preparation). Others have described alternate methods for RNA extraction (e.g., Kruhoffer et al., 2007; Kim et al., 2007; Marteau et al., 2005; Tang et al., 2003, and Whitney et al., 2003). Similarly, Rogers et al. (2006) have described methods for preparation of blood samples that yield material suitable for assessment of competence of Aβ binding to erythrocytes—which was found to be modulated by disease state. Although the erythrocyte fraction is frequently overlooked, this paper suggests it is also worthy of attention.

    The bottom line is that routine ways in which blood samples are collected and processed for future study are often inapplicable to important methods. In the design of future studies, attention must be given to recent developments in collecting, processing, storing, and analyzing blood samples.

    References:

    . Effects of storage, RNA extraction, genechip type, and donor sex on gene expression profiling of human whole blood. Clin Chem. 2007 Jun;53(6):1038-45. PubMed.

    . Isolation of microarray-grade total RNA, microRNA, and DNA from a single PAXgene blood RNA tube. J Mol Diagn. 2007 Sep;9(4):452-8. PubMed.

    . Collection and storage of human blood cells for mRNA expression profiling: a 15-month stability study. Clin Chem. 2005 Jul;51(7):1250-2. PubMed.

    . Peripheral clearance of amyloid beta peptide by complement C3-dependent adherence to erythrocytes. Neurobiol Aging. 2006 Dec;27(12):1733-9. PubMed.

    . Blood gene expression profiling of neurologic diseases: a pilot microarray study. Arch Neurol. 2005 Feb;62(2):210-5. PubMed.

    . Individuality and variation in gene expression patterns in human blood. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1896-901. PubMed.