Abstract
A localized acute phase response occurs in the brain in Alzheimer's disease. Acute phase proteins have previously been measured in brain homogenates to quantify this response. The extent to which measurements of these proteins reflect brain parenchymal contents, as opposed to vascular contents, is unknown. In this study, the acute phase proteins ceruloplasmin (CP), complement factor 3 (C3), haptoglobin (HP), and albumin were measured in regional brain homogenates from phosphate buffered saline-perfused and sham-perfused rats (n = 7–9/group). Interleukin 1-β (IL1-β) and copper were also measured. Mean CP, C3, HP, and albumin concentrations in perfused specimens decreased by 94%, 88%, 90%, and 81% vs. sham-perfused specimens (all p < 0.001), while ILl-β and copper were unchanged. These results suggest that acute phase protein measurements in brain homogenates reflect primarily vascular contents. However, IL1-β and copper concentrations in brain homogenates are minimally influenced by vascular contents.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Kushner, I. 1982. The phenomenon of the acute phase response. Ann. N.Y. Acad. Sci., 389:39–48.
Koj, A. 1985. Definition and classification of acute phase proteins. Pages 139–232, in Gordon, A. H., and Koj, A. (eds.). The Acute Phase Response in Injury and Infection, vol. 10, Elsevier, Amsterdam.
Baumann, H., Prowse, K. R., Marinkovic, S., Won, K.-A., and Jahreis, G. P. 1989. Stimulation of hepatic acute phase response by cytokines and glucocorticoids. Ann. N.Y. Acad. Sci., 557:280–296.
Abraham, C. R., and Potter, H. P. 1989. The protease inhibitor, α-1-antichymotrypsin, is a component of the brain amyloid deposits in normal aging and Alzheimer's disease. Ann. Med., 21:77–81.
Eikelenboom, P., Hack, C. E., Rozemuller, J. M., and Stam, F. C. 1989. Complement activation in amyloid plaques in Alzheimer's dementia. Virchows Archiv. B Cell Path., 56:259–262.
Bauer, J., Strauss, S., Schreiter-Gasser, U., Ganter, U., Schlegel, P., Witt, I., Yolk, B., and Berger, M. 1991. Interleukin-6 and α-2-macroglobulin indicate an acute-phase state in Alzheimer's disease cortices. FEBS Lett., 285:111–114.
Loeffler, D. A., LeWitt, P. A., Juneau, P. L., Sima, A. A. F., Nguyen, H.-U., DeMaggio, A. J., Brickman, C. M., Brewer, G. J., Dick, R. D., and Kanaley, L. 1996. Increased ceruloplasmin concentrations in Alzheimer's and Parkinson's disease brain regions. Brain Res., 738:265–274.
Sheng, J. G., Mrak, R. E., and Griffin, W. S. T. 1995. Microglial interleukin-1-α expression in brain regions in Alzheimer's disease: correlation with neuritic plaque distribution. Neuropath. Appl. Neurobiol., 21:290–301.
Sheng, J. G., Mrak, R. E., and Griffin, W. S. T. 1997. Glialneuronal interactions in Alzheimer disease: progressive association of IL-1-α+ microglia and S100-β+ astrocytes with neurofibrillary tangle stages. J. Neuropath. Exp. Neurol., 56:285–290.
Wood, J. A., Wood, P. L. L., Ryan, R., Graff-Radford, N. R., Pilapil, C., Robitaille, Y., and Quirion, R. 1993. Cytokine indices in Alzheimer's temporal cortex: no changes in mature IL-1β or IL-1RA but increases in the associated acute phase proteins IL-6, α2-macroglobulin and C-reactive protein. Brain Res., 629:245–252.
Middleton, R. B., and Linder, M. C. 1993. Synthesis and turnover of ceruloplasmin in rats treated with 17-β estradiol. Arch. Biochem. Biophys., 302:362–368.
Baumann, H. 1988. Electrophoretic analysis of acute phase plasma proteins. Methods Enzymol., 163:566–594.
Tran, T. N., Schaffer, K. J., Eubanks, S., Zhou, C. Y. I., and Linder, M. C. 1997. Secretion of ferritin by rat hepatoma cells and its regulation by inflammatory cytokines and iron. Blood, 90:4979–4986.
Linder, M., and Hazegh-Azam, M. 1996. The biochemistry and molecular biology of copper. Am. J. Clin. Nutr., (supplement) 63:797S-811S.
Cleveland, W. S. 1993. Visualizing Data, pages 25–27, Hobart Press, Summit.
Fairbanks, V. F. 1976. Hemoglobin, hemoglobin derivatives and myoglobin. Pages 411–414, in Tietz, N. W. (ed.), Fundamentals of Clinical Chemistry, W. B. Saunders, Philadelphia.
Aldred, A. R., Brack, C. M., and Schreiber, G. 1995. The cerebral expression of plasma protein genes in different species. Comp. Biochem. Physiol., 111B:1–15.
Connor, J. R., Tucker, P., Johnson, M., and Snyder, B. 1993. Ceruloplasmin levels in the human superior temporal gyrus in aging and Alzheimer's disease. Neurosci. Lett., 159:88–90.
Terai, K., Walker, D. G., McGeer, E. G., and McGeer, P. L. 1997. Neurons express proteins of the classical complement pathway in Alzheimer disease. Brain Res., 769:385–390.
Dickson, D., and Rogers, J. 1992. Neuroimmunology of Alzheimer's disease: a conference report. Neurobiol. Aging 13:793–798.
Walker, D. G., and McGeer, P. L. 1992. Complement gene expression in human brain: comparison between normal and Alzheimer disease cases. Mol. Brain. Res., 14:109–116.
Henry, J. B. 1991. Clinical Diagnosis and Management by Laboratory Methods, Pages 1367–1372. W. B. Saunders Co., Philadelphia.
van Deuren, M., van der Ven-Jongekrijg, J., Vannier, E., van Dalen, R., Pesman, G., Bartelink, A. K. M., Dinarello, C. A., and van der Meer, J. W. M. 1997. The pattern of interleukin-1β (IL-1β) and its modulating agents IL-1 receptor antagonist and IL-1 soluble receptor type II in acute meningococcal infections. Blood, 90:1101–1108.
Jacobs, D. S., Kasten, B. L. Jr., DeMott, W. R., and Wolfson, W. L. 1984. Laboratory Test Handbook with DRG Index, Page 376, Mosby/Lexi-Comp, St. Louis.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Loeffler, D.A., Linder, M.C., Zamany, M. et al. Measurement of Acute Phase Proteins in the Rat Brain: Contribution of Vascular Contents. Neurochem Res 24, 1313–1317 (1999). https://doi.org/10.1023/A:1020989426694
Issue Date:
DOI: https://doi.org/10.1023/A:1020989426694