. Finally, samples should be stored at −80˚C awaiting assay and multiple freeze-thaw cycles should be avoided to prevent sample degradation.

This study suffered several limitations, including assessment of only individuals with a diagnosis of Alzheimer’s Disease. However, while individuals with Alzheimer’s has been shown to have altered concentrations of a number of serum and plasma proteins relative to controls, there is no reason to suspect that Alzheimer’s disease alters the correlation between plasma and serum concentrations of individual proteins. In addition, a relatively small number of proteins were measured. Nevertheless, as the degree of correlation between plasma and serum concentrations was not part of the criteria for selection of proteins for the panel; we anticipate that our results are generalizable for the majority of proteins. We would therefore anticipate that the concentrations of less than half of all proteins are highly correlated (r2 > 0.75) between serum and plasma.

Some of the uncertainty surrounding the relationship of certain proteins to Alzheimer’s disease pathophysiology may be due to a lack of standardized protocols for protein measurement, particularly which blood fraction (plasma or serum) is assessed. The fraction of blood measured (plasma vs. serum) can have a large impact on the observed concentration of some proteins. Some of these differences were anticipated; clotting factors were lower and platelet-bound proteins higher in serum, relative to plasma. However, many others were not expected to differ to the degree observed, including several proteins that are of great interest in Alzheimer’s disease. Examples of such proteins include interleukin 6, tumor necrosis factor-alpha, and interferon gamma and granulocyte colony stimulating factor. These findings point out the need for research specifically aimed at identification of the most appropriate medium for examining particular biomarkers. Such an effort would, in the long run, be aimed at the development of standardized protocols to be utilized across research groups and projects in an effort to better understand biomarkers of AD.

5. ACKNOWLEDGEMENTS

This study was made possible by the Texas Alzheimer’s Research and Care Consortium (TARCC) funded by the state of Texas through the Texas Council on Alzheimer’s disease and Related Disorders. Research reported in this publication was also supported in part by the National Institute on Aging of the National Institutes of Health. Investigators at the University of Texas Southwestern Medical Center at Dallas (GX, RMH) acknowledge support from the UTSW Alzheimer’s disease Center; NIH, NIA grant P30AG12300. Investigators at the University of North Texas Health Science Center at Dallas (SEO) acknowledge support from NIA, NIA grant R01AG039389. The investigators would also like to thank Drs. Ralph McDade and Sam LaBrie with Myriad Rules Based Medicine. The content is solely the responsibility of the authors and does not necessarily represent the official views of any funding agency, including the National Institutes of Health.

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Appendix 1

NOTES

*The Texas Alzheimer’s Research Consortium: Investigators from the Texas Alzheimer’s Research and Care Consortium: Baylor College of Medicine: Rachelle Doody, MD, PhD, Violeta Capriles, Eveleen Darby, Tracey Evans; Texas Tech University Health Science Center: Benjamin Williams, MD, Yan Zhang, Gregory Schrimsher, Andrew Dentino, Ronnie Orozco, Merena Tindall; University of North Texas Health Science Center: Sid E. O’Bryant, Thomas Fairchild, PhD, Janice Knebl, DO, James R. Hall, PhD, Robert C. Barber, Douglas Mains, Lisa Alvarez; University of Texas Southwestern Medical Center: Perrie Adams, Roger Rosenberg, Joan Reisch, Ryan Huebinger, Guanghua Xiao, PhD, Doris Svetlik, Amy Werry, Janet Smith; University of Texas Health Science Center—San Antonio: Donald Royall, MD, Raymond Palmer, Marsha Polk.

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