AAD  Vol.1 No.3 , December 2012
Comparison of protein concentrations in serum versus plasma from Alzheimer’s patients
ABSTRACT
Background: There is great interest in developing blood-based biomarkers for Alzheimer’s disease (AD); however, there is no consensus as to what blood fraction is most appropriate for analyzing particular markers. The current study provides empirical evidence regarding how blood-based proteins vary depending on whether they are assayed in serum or plasma. Methods: Weanalyzed concentrations of 100 proteins in matched samples of serum and plasma from 39 Caucasian AD participants from the Texas Alzheimer’s Research and Care Consortium bymultiplex immunoassay. Results: Concentrations of 40 proteins were highly correlated (r2≥ 0.75) between plasma and serum while the remaining proteins were moderately to weakly correlated (r2< 0.75). Discussion: Whether plasma vs. serum is assayed can have a large impact on the observed concentration of some proteins, including several proteins that are of great interest to AD pathophysiology. The current findings may explain the significant discrepancies often times reported in the AD biomarker field.

Cite this paper
Huebinger, R., Xiao, G., Wilhelmsen, K., Diaz-Arrastia, R., Zhang, F., O'Bryant, S. and Barber, R. (2012) Comparison of protein concentrations in serum versus plasma from Alzheimer’s patients. Advances in Alzheimer's Disease, 1, 51-58. doi: 10.4236/aad.2012.13007.
References
[1]   Shaw, L.M., Korecka, M., Clark, C.M., Lee, V.M. and Trojanowski, J.Q. (2007) Biomarkers of neurodegeneration for diagnosis and monitoring therapeutics. Nature Reviews Drug Discovery, 6, 295-303. doi:10.1038/nrd2176

[2]   Thal, L.J., Kantarci, K., Reiman, E.M., Klunk, W.E., Weiner, M.W., Zetterberg, H., Galasko, D., Pratico, D., Griffin, S., Schenk, D. and Siemers, E. (2006) The role of biomarkers in clinical trials for Alzheimer disease. Alzheimer Disease and Associated Disorders, 20, 6-15. doi:10.1097/01.wad.0000191420.61260.a8

[3]   Mayeux, R., Honig, L.S., Tang, M.X., Manly, J., Stern, Y., Schupf, N. and Mehta, P.D. (2003) Plasma A[beta]40 and A[beta]42 and Alzheimer’s disease: Relation to age, mortality, and risk. Neurology, 61, 1185-1190. doi:10.1212/01.WNL.0000091890.32140.8F

[4]   Luis, C.A., Abdullah, L., Paris, D., Quadros, A., Mullan, M., Mouzon, B., Ait-Ghezala, G. and Crawford, F. (2009) Serum beta-amyloid correlates with neuropsychological impairment. Aging, Neuropsychology, and Cognition: A Journal on Normal and Dysfunctional Development, 16, 203-218. doi:10.1080/13825580802411766

[5]   Laske, C., Stransky, E., Leyhe, T., Eschweiler, G.W., Wittorf, A., Richartz, E., Bartels, M., Buchkremer, G. and Schott, K. (2006) Stage-dependent BDNF serum concentrations in Alzheimer’s disease. Journal of Neural Transmission, 113, 1217-1224. doi:10.1007/s00702-005-0397-y

[6]   O’Bryant, S.E., Hobson, V.L., Hall, J.R., Barber, R.C., Zhang, S., Johnson, L. and Diaz-Arrastia, R. (2011) Serum brain-derived neurotrophic factor levels are specifically associated with memory performance among Alzheimer’s disease cases. Dementia and Geriatric Cognitive Disorders, 31, 31-36. doi:10.1159/000321980

[7]   Waring, S., O’Bryant, S.E., Reisch, J.S., Diaz-Arrastia, R., Knebl, J. and Doody, R. (2008) The Texas Alzheimer’s Research Consortium longitudinal research cohort: Study design and baseline characteristics. Texas Public Health Journal, 60, 9-13.

[8]   McKhann, D., Drockman, D. and Folstein, M., et al. (1984) Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group. Neurology, 34, 939-944. doi:10.1212/WNL.34.7.939

[9]   R Development Core Team (2009) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, 409.

[10]   Zhang, F. and Drabier, R. (2012) IPAD: The integrated pathway analysis database for systematic enrichment analysis. BMC Bioinformatics, 13, S7. doi:10.1186/1471-2105-13-S15-S7

[11]   Mehta, C.R., Patel, N.R. and Tsiatis, A.A. (1984) Exact significance testing to establish treatment equivalence with ordered categorical data. Biometrics, 40, 819-825. doi:10.2307/2530927

[12]   Komulainen, P., Lakka, T.A., Kivipelto, M., Hassinen, M., Penttila, I.M., Helkala, E.L., Gylling, H., Nissinen, A. and Rauramaa, R. (2007) Serum high sensitivity C-reactive protein and cognitive function in elderly women. Age & Ageing, 36, 443-448. doi:10.1093/ageing/afm051

[13]   Schmidt, R., Schmidt, H., Curb, J.D., Masaki, K., White, L.R. and Launer, L.J. (2002) Early inflammation and dementia: A 25-year follow-up of the Honolulu-Asia aging study. Annals of Neurology, 52, 168-174. doi:10.1002/ana.10265

[14]   Newman, A.B., Fitzpatrick, A.L., Lopez, O., Jackson, S., Lyketsos, C., Jagust, W., Ives, D., Dekosky, S.T. and Kuller, L.H. (2005) Dementia and Alzheimer’s disease incidence in relationship to cardiovascular disease in the cardiovascular health study cohort. Journal of the American Geriatrics Society, 53, 1101-1107. doi:10.1111/j.1532-5415.2005.53360.x

[15]   Engelhart, M.J., Geerlings, M.I., Meijer, J., Kiliaan, A., Ruitenberg, A., van Swieten, J.C., Stijnen, T., Hofman, A., Witteman, J.C.M. and Breteler, M.M.B. (2004) Inflammatory proteins in plasma and the risk of dementia: The Rotterdam study. Archives of Neurology, 61, 668-672. doi:10.1001/archneur.61.5.668

[16]   Wright, C.B., Sacco, R.L., Rundek, T.R., Delman, J.B., Rabbani, L.E. and Elkind, M.S.V. (2006) Interleukin-6 is associated with cognitive function: The Northern Manhattan study. Journal of Stroke and Cerebrovascular Disease, 15, 34-38. doi:10.1016/j.jstrokecerebrovasdis.2005.08.009

[17]   Yaffe, K., Lindquist, K., Penninx, B.W., Simonsick, E.M., Pahor, M., Kritchevsky, S., Launer, L., Kuller, L., Rubin, S. and Harris, T. (2003) Inflammatory markers and cognition in well-functioning African-American and white elders. Neurology, 61, 76-80. doi:10.1212/01.WNL.0000073620.42047.D7

[18]   Bruunsgaard, H., Andersen-Ranberg, K., Jeune, B., Pedersen, A.N., Skinhoj, P. and Pedersen, B.K. (1999) A high plasma concentration of TNF-alpha is associated with dementia in centarians. Journal of Gerentology Series A: Biological Sciences Medical Sciences, 54, M357- M364. doi:10.1093/gerona/54.7.M357

[19]   Dik, M.G., Jonker, C., Hack, C.E., Smit, J.H., Comijs, H.C. and Eikelenboom, P. (2005) Serum inflammatory proteins and cognitive decline in older persons. Neurology, 64, 1371-1377. doi:10.1212/01.WNL.0000158281.08946.68

[20]   O’Bryant, S.E., Hobson, V.L., Hall, J.R., Barber, R.C., Zhang, S., Johnson, L. and Diaz-Arrastia, R. (2011) Serum brain-derived neurotrophic factor levels are specifically associated with memory performance among Alzheimer’s disease cases. Dementia and Geriatric Cognitive Disorders, 31, 31-36. doi:10.1159/000321980

[21]   O’Bryant, S.E., Xiao, G., Barber, R., Huebinger, R., Wilhelmsen, K., Edwards, M., Graff-Radford, N., Doody, R. and Diaz-Arrastia, R. (2011) A blood-based screening tool for Alzheimer’s disease that spans serum and plasma: Findings from TARC and ADNI. PLOS One, 6, e28092. doi:10.1371/journal.pone.0028092

 
 
Top