Skip to main content
SpringerLink
Log in

Clusterin and Alzheimer’s Disease

  • Chapter
Book cover Alzheimer’s Disease

Part of the book series: Subcellular Biochemistry ((SCBI,volume 38))

Abstract

Clusterin (apolipoprotein J) is a ubiquitous multifunctional glycoprotein with the capability to interact with a broad spectrum of molecules, among them the Alzheimer’s Aβ peptide. Due to its colocalization with fibrillar deposits in systemic and cerebral amyloid disorders, clusterin is also considered an amyloid-associated protein. Although no genuine function has been attributed to this protein so far, it has been implicated in a wide variety of physiological and pathological processes, a role that may vary according to the protein maturation, sub-cellular localization, and the presence of certain tissue- or cell-specific factors. This review focuses on the importance of clusterin in health and disease conditions, with particular emphasis in its role in Aβ amyloidosis and other disorders of protein folding.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aronow, B.J., Lund, S.D., Brown, T.L., Harmony, J.A., and Witte, D.P., 1993, Apolipoprotein J expression at fluid-tissue interfaces: potential role in barrier cytoprotection. Proc. Natl. Acad. Sci. USA 90: 725–729.

    PubMed  CAS  Google Scholar 

  • Bailey, R.W., Aronow, B., Harmony, J.A., and Griswold, M.D., 2002, Heat shock-initiated apoptosis is accelerated and removal of damaged cells is delayed in the testis of clusterin/ApoJ knock-out mice. Biol Reprod. 66: 1042–1053.

    PubMed  CAS  Google Scholar 

  • Bailey, R.W., Dunker, A.K., Brown, C.J., Garner, E.C., and Griswold, M.D., 2001, Clusterin, a binding protein with a molten globule-like region. Biochemistry 40: 11828–11840.

    PubMed  CAS  Google Scholar 

  • Bales, K.R., Verina, T., Cummins, D.J., Du, Y., Dodel, R.C., Saura, J., Fishman, C.E., DeLong, C.A., Piccardo, P., Petegnief, V., Ghetti, B., and Paul, S.M., 1999, Apolipoprotein E is essential for amyloid deposition in the APP(V717F) transgenic mouse model of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 96: 15233–15238.

    PubMed  CAS  Google Scholar 

  • Bales, K.R., Verina, T., Dodel, R.C., Du, Y., Altstiel, L., Bender, M., Hyslop, P., Johnstone, E.M., Little, S.P., Cummins, D.J., Piccardo, P., Ghetti, B., and Paul, S.M., 1997, Lack of apolipoprotein E dramatically reduces amyloid beta-peptide deposition. Nature Genet. 17: 263–264.

    PubMed  CAS  Google Scholar 

  • Bartl, M.M., Luckenbach, T., Bergner, O., Ullrich, O., and Koch-Brandt, C., 2001, Multiple receptors mediate apoJ-dependent clearance of cellular debris into nonprofessional phagocytes. Ex.p. Cell. Res. 271: 130–141.

    CAS  Google Scholar 

  • Blaschuk, O., Burdzy, K., and Fritz, I.B., 1983, Purification and characterization of a cell-aggregating factor (clusterin), the major glycoprotein in ram rete testis fluid. J. Bio. Chem. 258: 7714–7720.

    CAS  Google Scholar 

  • Boggs, L.N., Fuson, K.S., Baez, M., Churgay, L., McClure, D., Becker, G., and May, P.C., 1996, Clusterin (Apo J) protects against in vitro amyloid-beta (1-40) neurotoxicity. J. Neurochem. 67: 1324–1327.

    PubMed  CAS  Google Scholar 

  • Brett, J., Schmidt, A.M., Yan, S.D., Zou, Y.S., Weidman, E., Pinsky, D., Nowygrod, R., Neeper, M., Przysiecki, C., Shaw, A., Migheli, A., and Stern, D., 1993, Survery of the distribution of a newly characterized receptor for advanced glycation end products in tissues. Am. J. Pathol. 143: 1699–1712.

    PubMed  CAS  Google Scholar 

  • Burkey, B.F., Stuart, W.D., and Harmony, J.A., 1992, Hepatic apolipoprotein J is secreted as a lipoprotein. J. Lipid Re.s 33: 1517–1526.

    CAS  Google Scholar 

  • Buttyan, R., Olsson, C.A., Pintar, J., Chang, C., Bandyk, M., Ng, P.Y., and Sawczuk, I.S., 1989, Induction of the TRPM-2 gene in cells undergoing programmed death. Mol. Cell Biol. 9: 3473–3481.

    PubMed  CAS  Google Scholar 

  • Calero, M., Rostagno, A., Matsubara, E., Zlokovic, B., Frangione, B., and Ghiso, J., 2000, Apolipoprotein J (clusterin) and Alzheimer’s disease. Microsc. Res. Tech. 50: 305–315.

    PubMed  CAS  Google Scholar 

  • Calero, M., Tokuda, T., Rostagno, A., Kumar, A., Zlokovic, B., Frangione, B., and Ghiso, J., 1999, Functional and structural properties of lipid-associated apolipoprotein J (clusterin). Biochem. J. 344: 375–383.

    PubMed  CAS  Google Scholar 

  • Choi-Miura, N.H., Ihara, Y., Fukuchi, K., Takeda, M., Nakano, Y., Tobe, T., and Tomita, M., 1992, SP-40,40 is a constituent of Alzheimer’s amyloid. Acta Neuropathol. (Berl.) 83: 260–264.

    CAS  Google Scholar 

  • Christie, D.L., Freeman, M., and Hyman, B.T., 1996, Expression of the macrophage scavenger receptor, a multifunctional lipoprotein receptor, in microglia associated with senile plaques in Alzheimer’s disease. Am. J. Pathol. 148: 399–403.

    PubMed  CAS  Google Scholar 

  • Collard, M.W., and Griswold, M.D., 1987, Biosynthesis and molecular cloning of sulfated glycoprotein 2 secreted by rat Sertoli cells. Biochemistry 26: 3297–3303.

    PubMed  CAS  Google Scholar 

  • Danik, M., Chabot, J.G., Hassan-Gonzalez, D., Suh, M., and Quirion, R., 1993, Localization of sulfated glycoprotein-2/clusterin mRNA in the rat brain by in situ hybridization. J. Comp. Neurol. 334: 209–227.

    PubMed  CAS  Google Scholar 

  • Danik, M., Chabot, J.G., Mercier, C., Benabid, A.L., Chauvin, C., Quirion, R., and Suh, M., 1991, Human gliomas and epileptic foci express high levels of a mRNA related to rat testicular sulfated glycoprotein 2, a purported marker of cell death. Proc. Natl. Acad. Sci. USA 88:8577–8581.

    PubMed  CAS  Google Scholar 

  • de Silva, H.V., Harmony, J.A., Stuart, W.D., Gil, C.M., and Robbins, J., 1990a, Apolipoprotein J: structure and tissue distribution. Biochemistry 29: 5380–5389.

    PubMed  Google Scholar 

  • de Silva, H.V., Stuart, W.D., Park, Y.B., Mao, S.J., Gil, C.M., Wetterau, J.R., Busch, S.J., and Harmony, J.A., 1990b, Purification and characterization of apolipoprotein J. J. Biol. Chem. 265: 14292–14297.

    PubMed  Google Scholar 

  • de Silva, H.V., Stuart, W.D., Duvic, C.R., Wetterau, J.R., Ray, M.J., Ferguson, D.G., Albers, H.W., Smith, W.R., and Harmony, J.A., 1990c, A 70-kDa apolipoprotein designated ApoJ is a marker for subclasses of human plasma high density lipoproteins. J. Biol. Chem. 265: 13240–13247.

    PubMed  Google Scholar 

  • Deane, R., Du Yan, S., Submamaryan, R.K., LaRue, B., Jovanovic, S., Hogg, E., Welch, D., Manness, L., Lin, C., Yu, J., Zhu, H., Ghiso, J., Frangione, B., Stern, A., Schmidt, A.M., Armstrong, D.L., Arnold, B., Liliensiek, B., Nawroth, P., Hofman, F., Kindy, M., Stern, D., and Zlokovic, B., 2003, RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nature Med. 9: 907–913.

    PubMed  CAS  Google Scholar 

  • Debure, L., Vayssiere, J.L., Rincheval, V., Loison, F., Le Drean, Y., and Michel, D., 2003, Intracellular clusterin causes juxtanuclear aggregate formation and mitochondrial alteration. J. Cell Sci. 116: 3109–3121.

    PubMed  CAS  Google Scholar 

  • DeMattos, R.B., O’Dell M, A., Parsadanian, M., Taylor, J.W., Harmony, J.A., Bales, K.R., Paul, S.M., Aronow, B.J., and Holtzman, D.M., 2002, Clusterin promotes amyloid plaque formation and is critical for neuritic toxicity in a mouse model of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 99: 10843–10848.

    PubMed  CAS  Google Scholar 

  • DeMattos, R.B., Cirrito, J., Parsadanian, M., May, P.C., O’Dell, M.A., Taylor, J.W., Harmony, J.A., Aronow, B., Bales, K.R., Paul, S.M., and Holtzman, D., 2004, ApoE and clusterin cooperatively suppress Ab levels and deposition: Evidence that apoE regulates extracellular Ab metabolism in vivo. Neuron 41: 193–202.

    PubMed  CAS  Google Scholar 

  • El Khoury, J., Hickman, S.E., Thomas, C.A., Cao, L., Silverstein, S.C., and Loike, J.D., 1996, Scavenger receptor-mediated adhesion of microglia to beta-amyloid fibrils. Nature 382: 716–719.

    PubMed  Google Scholar 

  • French, L.E., Chonn, A., Ducrest, D., Baumann, B., Belin, D., Wohlwend, A., Kiss, J.Z., Sappino, A.P., Tschopp, J., and Schifferli, J.A., 1993, Murine clusterin: molecular cloning and mRNA localization of a gene associated with epithelial differentiation processes during embryogenesis. J. Cell Biol. 122: 1119–1130.

    PubMed  CAS  Google Scholar 

  • Fritz, I.B., Burdzy, K., Setchell, B., Blaschuk, O., Lyon, M.F., and Setchell, B.P., 1983, Ram rete testis fluid contains a protein (clusterin) which influences cell-cell interactions in vitro. Evidence for a defective seminiferous tubule barrier in testes of Tfm and Sxr mice. Biol. Reprod. 28: 1173–1188.

    PubMed  CAS  Google Scholar 

  • Games, D., Adams, D., Alessandrini, R., Barbour, R., Berthelette, P., Blackwell, C., Carr, T., Clemens, J., Donaldson, T., Gillespie, F., and et al., 1995, Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature 373: 523–527.

    PubMed  CAS  Google Scholar 

  • Ghiso, J., and Frangione, B., 2002, Amyloidosis and Alzheimer’s disease. Adv. Drug Deliv. Rev. 54: 1539–1551.

    PubMed  CAS  Google Scholar 

  • Ghiso, J., Matsubara, E., Koudinov, A., ChoiMiura, N.H., Tomita, M., Wisniewski, T., and Frangione, B., 1993, The cerebrospinalfluid soluble formof Alzheimer’s amyloid beta is complexed to SP40,40 (apolipoprotein J), an inhibitor of the complement membrane attack complex. Biochem. J. 293: 27–30.

    PubMed  CAS  Google Scholar 

  • Giannakipoulos, P., Kovari, E., French, L., Viard, I., Hof, P.R., and Bouras, C., 1998, Possible neuroprotective role of clusterin in Alzheimer’s disease: a quantitative immunocytochemical study. Acta Neuropathol. (Berl.) 95: 387–394.

    Google Scholar 

  • Gutacker, C., Klock, G., Diel, P., and Koch-Brandt, C., 1999, Nerve growth factor and epidermal growth factor stimulate clusterin gene expression in PC 12 cells. Biochem. J. 339: 759–766.

    PubMed  CAS  Google Scholar 

  • Hammad, S.M., Ranganathan, S., Loukinova, E.B., Twal, W.O., and Argraves, W.S., 1997, Interaction of apolipoprotein J-amyloid beta-peptide complex with low density lipoprotein receptor-related protein-2/megalin. A mechanism to prevent pathological accumulation of amyloid beta-peptide. J. Biol. Chem. 272: 18644–18649.

    PubMed  CAS  Google Scholar 

  • Han, B.H., DeMattos, R.B., Dugan, L.L., Kim-Han, J.S., Brendza, R.P., Fryer, J.D., Kierson, M., Cirrito, J., Quick, K., Harmony, J.A., Aronow, B., and Holtzman, D., 2001, Clusterin contributes to caspase-3 independent brain injury following neonatal hypoxia-ischemia. Nature Med. 7: 338–343.

    PubMed  CAS  Google Scholar 

  • Harr, S.D., Uint, L., Hollister, R., Hyman, B.T., and Mendez, A.J., 1996, Brain expression of apolipoproteins E, J, and A-I in Alzheimer’s disease. J. Neurochem. 66: 2429–2435.

    PubMed  CAS  Google Scholar 

  • Hatters, D.M., Wilson, M.R., Easterbrook-Smith, S.B., and Howlett, G.J., 2002, Suppression of apolipoprotein C-II amyloid formation by the extracellular chaperone, clusterin. Ear. J. Biochem. 269: 2789–2794.

    CAS  Google Scholar 

  • Herault, Y., Chatelain, G., Brun, G., and Michel, D., 1992, V-src-induced-transcription of the avian clusterin gene. Nucleic Acids Res. 20: 6377–6383.

    PubMed  CAS  Google Scholar 

  • Hochgrebe, T., Pankhurst, G.J., Wilce, J., and Easterbrook-Smith, S.B., 2000, pH-dependent changes in the in vitro ligand-binding properties and structure of human clusterin. Biochemistry 39: 1411–1419.

    PubMed  CAS  Google Scholar 

  • Hochgrebe, T.T., Humphreys, D., Wilson, M.R., and Easterbrook-Smith, S.B., 1999, A reexamination of the role of clusterin as a complement regulator. Exp. Cell Res. 249: 13–21.

    PubMed  CAS  Google Scholar 

  • Humphreys, D., Hochgrebe, T.T., Easterbrook-Smith, S.B., Tenniswood, M.P., and Wilson, M.R., 1997, Effects of clusterin overexpression on TNF alpha-and TGF beta-mediated death of L929 cells. Biochemistry 36: 15233–15243.

    PubMed  CAS  Google Scholar 

  • Hussain, MM., Strickland, D.K., and Bakillah, A., 1999, The mammalian low-density lipoprotein receptor family. Ann.. Rev.. Nutr. 19: 141–172.

    CAS  Google Scholar 

  • Jenne, D.E., and Tschopp, J., 1989, Molecular structure and functional characterization of a human complement cytolysis inhibitor found in blood and seminal plasma: identity to sulfated glycoprotein 2, a constituent of rat testis fluid. Proc Natl Acad Sci USA 86: 7123–7127.

    PubMed  CAS  Google Scholar 

  • Jenne, D.E., Lowin, B., Peitsch, M.C., Bottcher, A., Schmitz, G., and Tschopp, J., 1991, Clusterin (complement lysis inhibitor) forms a high density lipoprotein complex with apolipoprotein A-I in human plasma. J. Biol. Chem. 266: 11030–11036.

    PubMed  CAS  Google Scholar 

  • Jin, G., and Howe, P.H., 1997, Regulation of clusterin gene expression by transforming growth factor beta. J. Biol. Chem. 272: 26620–26626.

    PubMed  CAS  Google Scholar 

  • Johnson, N.A., Sengupta, S., Saidi, S.A., Lessan, K., Charnock-Jones, S.D., Scott, L., Stephens, R., Freeman, T.C., Tom, B.D.M., Harris, M., Denyer, G., Sundaram, M., Sasisekharan, R., Smith, S.K., and Print, C.G., 2004, Endothelial cells preparing to die by apoptosis initiate a program of transcriptome and glycome regulation. Faseb J. 18: 188–190.

    PubMed  CAS  Google Scholar 

  • Jones, S.E., Meerabux, J.M., Yeats, D.A., and Neal, M.J., 1992, Analysis of differentially expressed genes in retinitis pigmentosas retinas. Altered expression of clusterin mRNA. FEBS Lett. 300:279–282.

    PubMed  CAS  Google Scholar 

  • Jordan, J., Galindo, M.F., Miller, R.J., Reardon, C.A., Getz, G.S., and LaDu, M.J., 1998, Isoform-specific effect of apolipoprotein E on cell survival and beta-amyloid-induced toxicity in rat hippocampal pyramidal neuronal cultures. J. Neurosci. 18: 195–204.

    PubMed  CAS  Google Scholar 

  • Kapron, J.T., Hilliard, G.M., Lakins, J.N., Tenniswood, M.P., West, K.A., Carr, S.A., and Crabb, J.W., 1997, Identification and characterization of glycosylation sites in human serum clusterin. Protein Sci. 6: 2120–2133.

    PubMed  CAS  Google Scholar 

  • Kida, E., Pluta, R., Lossinsky, A.S., Golabek, A., Choi-Miura, N.H., Wisniewski, H.E., and Mossakowski, M.J., 1995, Complete cerebral ischemia with short-term survival in rat induced by cardiac arrest. II. Extracellular and intracellular accumulation of apolipoproteins E and J in the brain. Brain Res. 674: 341–346.

    PubMed  CAS  Google Scholar 

  • Kimura, K., and Yamamoto, M., 1996, Modification of the alternative splicing process of testosterone-repressed prostate message-2 (TRPM-2) gene by protein synthesis inhibitors and heat shock treatment. Biochim. Biophys. Acta 1307: 83–88.

    PubMed  Google Scholar 

  • Kimura, K., Asami, K., and Yamamoto, M., 1997, Effect of heat shock treatment on the production of variant testosterone-repressed prostate message-2 (TRPM-2) mRNA in culture cells. Cell Biochem. Funct. 15: 251–257.

    PubMed  CAS  Google Scholar 

  • Kirszbaum, L., Bozas, S.E., and Walker, I.D., 1992, SP-40,40, a protein involved in the control of the complement pathway, possesses a unique array of disulphide bridges. FEES Lett. 297: 70–76.

    CAS  Google Scholar 

  • Kirszbaum, L., Sharpe, J.A., Murphy, B., d’Apice, A.J., Classon, B., Hudson, P., Walker, I.D., Leskov, K.S., Klokov, D.Y., Li, J., Kinsella, T.J., Boothman, D.A., Fritz, I.B., Burdzy, K., Setchell, B., Blaschuk, O., Slawin, K., Sawczuk, I.S., Olsson, C.A., Buttyan, R., Tobe, T., Minoshima, S., Yamase, S., Choi, N.H., Comity, M., Shimizu, N., Purrello, M., Bettuzzi, S., Di Pietro, C., Mirabile, E., Di Blasi, M., Rimini, R., Grzeschik, K.H., Ingletti, C., Coiti, A., Sichel, G., Wong, P., Taillefer, D., Lakins, J., Pineault, J., Chader, G., and Tenniswood, M., 1989, Molecular cloning and characterization of the novel, human complement-associated protein, SP-40,40: a link between the complement and reproductive systems. EMBO J. 8: 711–718.

    PubMed  CAS  Google Scholar 

  • Koudinov, A., Matsubara, E., Frangione, B., and Ghiso, J., 1994, The soluble form of Alzheimer’s amyloid beta protein is complexed to high density lipoprotein 3 andvery high density lipoprotein in normal human plasma. Biochem. Biophys. Res. Commun. 205: 1164–1171.

    PubMed  CAS  Google Scholar 

  • Koudinov, A., Koudinova, N., Kumar, A., Beavis, R.C., and Ghiso, J., 1996, Biochemical characterization of Alzheimer’s soluble amyloid beta protein in human cerebrospinal fluid: Association with high density lipoproteins. Biochem. Biophys. Res. Commun. 223: 592–597.

    PubMed  CAS  Google Scholar 

  • Kounnas, M.Z., Loukinova, E.B., Stefansson, S., Harmony, J.A., Brewer, B.H., Strickland, D.K., and Argraves, W.S., 1995, Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin. J. Biol. Chem. 270: 13070–13075.

    PubMed  CAS  Google Scholar 

  • Lakins, J.N., Poon, S., Easterbrook-Smith, S.B., Carver, J.A., Tenniswood, M.P., and Wilson, M.R., 2002, Evidence that clusterin has discrete chaperone and ligand binding sites. Biochemistry 41: 282–291.

    PubMed  CAS  Google Scholar 

  • Lambert, M.P., Barlow, A.K., Chromy, B.A., Edwards, C., Freed, R., Liosatos, M., Morgan, T.E., Rozovsky, I., Trommer, B., Viola, K.L., Wals, P., Zhang, C., Finch, C.E., Krafft, G.A., and Klein, W.L., 1998, Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc. Natl. Acad. Sci. USA 95: 6448–6453.

    PubMed  CAS  Google Scholar 

  • Lemansky, P., Brix, K., and Herzog, V., 1999, Subcellular distribution, secretion, and posttranslational modifications of clusterin in thyrocytes. Exp. Cell Res. 251: 147–155.

    PubMed  CAS  Google Scholar 

  • Leskov, K.S., Klokov, D.Y., Li, J., Kinsella, T.J., and Boothman, D.A., 2003, Synthesis and functional analyses of nuclear clusterin, a cell death protein. J. Biol. Chem. 278: 11590–11600.

    PubMed  CAS  Google Scholar 

  • Lidstrom, A.M., Bogdanovic, N., Hesse, C., Volkman, I., Davidsson, P., and Blennow, K., 1998, Clusterin (apolipoprotein J) protein levels are increased in hippocampus and in frontal cortex in Alzheimer’s disease. Exp. Neurol. 154: 511–521.

    PubMed  CAS  Google Scholar 

  • Lidstrom, A.M., Hesse, C., Rosengren, L., Fredman, P., Davidsson, P., and Blennow, K., 2001, Normal levels of clusterin in cerebrospinal fluid in Alzheimer’s disease, and no change after acute ischemic stroke. J. Alzheimers Dis. 3: 435–442.

    PubMed  CAS  Google Scholar 

  • Lucarelli, M., Gennarelli, M., Cardelli, P., Novelli, G., Scarpa, S., Dallapiccola, B., and Strom, R., 1997, Expression of receptors for native and chemically modified low-density lipoproteins in brain microvessels. FEBS Lett. 401: 53–58.

    PubMed  CAS  Google Scholar 

  • Mackic, J.B., Stins, M., McComb, J.G., Calero, M., Ghiso, J., Kim, K.S., Yan, S.D., Stern, D., Schmidt, A.M., Frangione, B., and Zlokovic, B.V., 1998, Human blood-brain barrier receptors for Alzheimer’s amyloid-beta 1-40. Asymmetrical binding, endocytosis, and transcytosis at the apical side of brain microvascular endothelial cell monolayer. J. Clin. Invest. 102: 734–743.

    PubMed  CAS  Google Scholar 

  • Manuelidis, L, Fritch, W., and Xi, Y.G., 1997, Evolution of a strain of CJD that induces BSE-like plaques. Science 277: 94–98.

    PubMed  CAS  Google Scholar 

  • Matsubara, E., Frangione, B., and Ghiso, J., 1995, Characterization of lipoprotein J Alzheimerrss A-beta interaction. J. Biol. Chem. 270: 7563–7567.

    PubMed  CAS  Google Scholar 

  • Matsubara, E., Soto, C., Governale, S., Frangione, B., and Ghiso, J., 1996, Apolipoprotein J and Alzheimer’s amyloid beta solubility. Biochem. J. 316: 671–679.

    PubMed  CAS  Google Scholar 

  • Matsubara, E., Ghiso, J., Frangione, B., Amari, M., Tomidokoro, Y., Ikeda, Y., Harigaya, Y., Okamoto, K., and Shoji, M., 1999, Lipoprotein-free amyloidogenic peptides in plasma are elevated in patients with sporadic Alzheimer’s disease and Down’s syndrome. Ann. Neurol. 45:537–541.

    PubMed  CAS  Google Scholar 

  • Matsuda, A., Itoh, Y., Koshikawa, N., Akizawa, T., Yana, I., and Seiki, M., 2003, Clusterin, an abundant serum factor, is a possible negative regulator of MT6-MMP/MMP-25 produced by neutrophils. J. Biol. Chem. 278: 36350–36357.

    PubMed  CAS  Google Scholar 

  • McGeer, P.L., Kawamata, T., and Walker, D.G., 1992, Distribution of clusterin in Alzheimer brain tissue. Brain Res. 579: 337–341.

    PubMed  CAS  Google Scholar 

  • McHattie, S., and Edington, N., 1999, Clusterin prevents aggregation of neuropeptide 106–126 in vitro. Biochem. Biophys. Res. Commun. 259: 336–340.

    PubMed  CAS  Google Scholar 

  • McHattie, S., Wells, G.A., Bee, J., and Edington, N., 1999, Clusterin in bovine spongiform encephalopathy (BSE). J. Comp. Pathol. 121: 159–171.

    PubMed  CAS  Google Scholar 

  • McLaughlin, L., Zhu, G., Mistry, M., Ley-Ebert, C., Stuart, W.D., Florio, C.J., Groen, P.A., Witt, S.A., Kimball, T.R., Witte, D.P., Harmony, J.A., and Aronow, B.J., 2000, Apolipoprotein J/clusterin limits the severity of murine autoimmune myocarditis. J. Clin. Invest. 106: 1105–1113.

    PubMed  CAS  Google Scholar 

  • Michel, D., Chatelain, G., Herault, Y., and Brun, G., 1995, The expression of the avian clusterin gene can be driven by two alternative promoters with distinct regulatory elements. Eur. J. Biochem. 229: 215–223.

    PubMed  CAS  Google Scholar 

  • Michel, D., Chatelain, G., North, S., and Brun, G., 1997, Stress-induced transcription of the clusterin/apoJ gene. Biochem. J. 328: 45–50.

    PubMed  CAS  Google Scholar 

  • Mitsuhashi, T., Li, Y.M., Fishbane, S., and Vlassara, H., 1997, Depletion of reactive advanced glycation endproducts from diabetic uremic sera using a lysozyme-linked matrix. J. Clin. Invest. 100: 847–854.

    PubMed  CAS  Google Scholar 

  • Murphy, B.F., Kirszbaum, L., Walker, I.D., and d’Apice, A.J., 1988, SP-40,40, a newly identified normal human serum protein found in the SC5b-9 complex of complement and in the immune deposits in glomerulonephritis. J. Clin. Invest. 81: 1858–1864.

    PubMed  CAS  Google Scholar 

  • Narita, M., Holtzman, D.M., Schwartz, A.L., and Bu, G., 1997, Alpha2-macroglobulin complexes with and mediates the endocytosis of beta-amyloid peptide via cell surface low-density lipoprotein receptor-related protein. J. Neurochem. 69: 1904–1911.

    PubMed  CAS  Google Scholar 

  • Nishida, K., Quantock, A.J., Dota, A., Choi-Miura, N.H., and Kinoshita, S., 1999, Apolipoproteins J and E co-localise with amyloid in gelatinous drop-like and lattice type I corneal dystrophies. Br. J. Ophthalmol. 83: 1178–1182.

    PubMed  CAS  Google Scholar 

  • O’Bryan, MX, Baker, H.W., Saunders, J.R., Kirszbaum, L., Walker, I.D., Hudson, P., Liu, D.Y., Glew, M.D., d’Apice, A.J., and Murphy, B.F., 1990, Human seminal clusterin (SP-40,40). Isolation and characterization. J. Clin. Invest. 85: 1477–1486.

    PubMed  CAS  Google Scholar 

  • Oda, T., Pasinetti, G.M., Osterburg, H.H., Anderson, C., Johnson, S.A., and Finch, C.E., 1994, Purification and characterization of brain clusterin. Biochem. Biophys. Res. Commun. 204: 1131–1136.

    PubMed  CAS  Google Scholar 

  • Oda, T., Wals, P., Osterburg, H.H., Johnson, S.A., Pasinetti, G.M., Morgan, T.E., Rozovsky, I., Stine, W.B., Snyder, S.W., Holzman, T.F., and et al., 1995, Clusterin (apoJ) alters the aggregation of amyloid beta-peptide (Abeta 1-42) and forms slowly sedimenting A beta complexes that cause oxidative stress. Exp. Neurol. 136: 22–31.

    PubMed  CAS  Google Scholar 

  • O’Sullivan, J., Whyte, L., Drake, J., and Tenniswood, M., 2003, Alterations in the post-translational modification and intracellular trafficking of clusterin in MCF-7 cells during apoptosis. Cell Death Differ. 10: 914–927.

    PubMed  CAS  Google Scholar 

  • Palmer, D.J., and Christie, D.L., 1992, Identification of molecular aggregates containing glycoproteins III, J, K (carboxypeptidase H), and H (Kex2-related proteases) in the soluble and membrane fractions of adrenal medullary chromaffin granules. J. Biol. Chem. 267: 19806–19812.

    PubMed  CAS  Google Scholar 

  • Pankhurst, G.J., Bennett, C.A., and Easterbrook-Smith, S.B., 1998, Characterization of the heparin-binding properties of human clusterin. Biochemistry 37: 4823–4830.

    PubMed  CAS  Google Scholar 

  • Pasinetti, G.M., Johnson, S.A., Oda, T., Rozovsky, I., and Finch, C.E., 1994, Clusterin (SGP-2): a multifunctional glycoprotein with regional expression in astrocytes and neurons of the adult rat brain. J. Comp. Neurol. 339: 387–400.

    PubMed  CAS  Google Scholar 

  • Polihronis, M., Paizis, K., Carter, G., Sedal, L., and Murphy, B., 1993, Elevation of human cerebrospinal fluid clusterin concentration is associated with acute neuropathology. J. Neurol. Sci. 115: 230–233.

    PubMed  CAS  Google Scholar 

  • Poon, S., Easterbrook-Smith, S.B., Rybchyn, M.S., Carver, J.A., and Wilson, M.R., 2000, Clusterin is an ATP-independent chaperone with very broad substrate specificity that stabilizes stressed proteins in a folding-competent state. Biochemistry 39: 15953–15960.

    PubMed  CAS  Google Scholar 

  • Poon, S., Treweek, T.M., Wilson, M.R., Easterbrook-Smith, S.B., and Carver, J.A., 2002a, Clusterin is an extracellular chaperone that specifically interacts with slowly aggregating proteins on their off-folding pathway. FEBS Lett. 513: 259–266.

    PubMed  CAS  Google Scholar 

  • Poon, S., Rybchyn, M.S., Easterbrook-Smith, S.B., Carver, J.A., Pankhurst, G.J., Wilson, M.R., Treweek, T.M., Lakins, J.N., and Tenniswood, M.P., 2002b, Mildly acidic pH activates the extracellular molecular chaperone clusterin. J.Biol. Chem. 277: 39532–39540.

    PubMed  CAS  Google Scholar 

  • Purrello, M., Bettuzzi, S., Di Pietro, C., Mirabile, E., Di Blasi, M., Rimini, R., Grzeschik, K.H., Ingletti, C., Corti, A., Sichel, G., Wong, P., Taillefer, D., Lakins, J., Pineault, J., Chader, G., and Tenniswood, M., 1991, The gene for SP-40,40, human homolog of rat sulfated glycoprotein 2, rat clusterin, and rat testosterone-repressed prostate message 2, maps to chromosome 8. Genomics 10: 151–156.

    PubMed  CAS  Google Scholar 

  • Qiu, Z., Strickland, D.K., Hyman, B.T., and Rebeck, G.W., 1999, Alpha2-macroglobulin enhances the clearance of endogenous soluble beta-amyloid peptide via low-density lipoprotein receptor-related protein in cortical neurons. J. Neurochem. 73: 1393–1398.

    PubMed  CAS  Google Scholar 

  • Rosenberg, M.E., Girton, R., Finkel, D., Chmielewski, D.H., Barie, A., III, Witte, D.P., Zhu, G., Bissler, J.J., Harmony, J.A., and Aronow, B., 2002, Apolipoprotein J/Clusterin prevents a progressive glomerulopathy of aging. Mol. Cell Biol. 22: 1893–1902.

    PubMed  CAS  Google Scholar 

  • Santilli, G., Aronow, B.J., and Sala, A., 2003, Essential requirement of apolipoprotein J (clusterin) signaling for IkappaB expression and regulation of NF-kappaB activity. J. Biol. Chem. 278: 38214–38219.

    PubMed  CAS  Google Scholar 

  • Sasaki, A., Shoji, M., Harigaya, Y., Kawarabayashi, T., Ikeda, M., Naito, M., Matsubara, E., Abe, K., and Nakazato, Y., 2002a, Amyloid cored plaques in Tg2576 transgenic mice are characterized by giant plaques, slightly activated microglia, and the lack of paired helical filament-typed, dystrophic neurites. Virchows Arch. 441: 358–367.

    PubMed  CAS  Google Scholar 

  • Sasaki, K., Doh-ura, K., Ironside, J.W., and Iwaki, T., 2002b, Increased clusterin (apolipoprotein J) expression in human and mouse brains infected with transmissible spongiform encephalopathies. Acta Neuropathol. (Berl.) 103: 199–208.

    CAS  Google Scholar 

  • Sasaki, N., Takeuchi, M., Chowei, H., Kikuchi, S., Hayashi, Y., Nakano, N., Ikeda, H., Yamagishi, S., Kitamoto, T., Saito, T., and Makita, Z., 2002c, Advanced glycation end products (AGE) and their receptor (RAGE) in the brain of patients with Creutzfeldt-Jakob disease with prion plaques. Neurosci. Lett. 326: 117–120.

    PubMed  CAS  Google Scholar 

  • Schreiber, S.S., Tocco, G., Najm, I., and Baudry, M., 1993, Seizure activity causes a rapid increase in sulfated glycoprotein-2 messenger RNA in the adult but not in the neonatal rat brain. Neurosci. Lett. 153: 17–20.

    PubMed  CAS  Google Scholar 

  • Shibata, M., Yamada, S., Kumar, S.R., Calero, M., Bading, J., Frangione, B., Holtzman, D.M., Miller, C.A., Strickland, D.K., Ghiso, J., and Zlokovic, B.V., 2000, Clearance of Alzheimer’s amyloid-ss(l-40) peptide from brain by LDL receptor-related protein-I at the blood-brain barrier. J. Clin. Invest. 106: 1489–1499.

    PubMed  CAS  Google Scholar 

  • Silkensen, J.R., Skubitz, K.M., Skubitz, A.P., Chmielewski, D.H., Manivel, J.C., Dvergsten. J.A., and Rosenberg, M.E., 1995, Clusterin promotes the aggregation and adhesion of renal porcine epithelial cells. J. Clin. Invest. 96: 2646–2653.

    PubMed  CAS  Google Scholar 

  • Slawin, K., Sawczuk, I.S., Olsson, C.A., Buttyan, R., Blaschuk, O., Burdzy, K., Fritz, I.B., Tobe, T., Minoshima, S., Yamase, S., Choi, N.H., Tomita, M., Shimizu, N., Purrello, M., Bettuzzi, S., Di Pietro, C., Mirabile, E., Di Blasi, M., Rimini, R., Grzeschik, K.H., Ingletti, C., Corti, A., Sichel, G., Wong, P., Taillefer, D., Lakins, J., Pineault, J., Chader, G., and Tenniswood, M., 1990, Chromosomal assignment of the human homologue encoding SGP-2. Biochem. Biophys. Res. Commun. 172: 160–164.

    PubMed  CAS  Google Scholar 

  • Stuart, W.D., Krol, B., Jenkins, S.H., and Harmony, J.A., 1992, Structure and stability of apolipoprotein J-containing high-density lipoproteins. Biochemistry 31: 8552–8559.

    PubMed  CAS  Google Scholar 

  • Sylvester, S.R., Morales, C., Oko, R., and Griswold, M.D., 1991, Localization of sulfated glycoprotein-2 (clusterin) on spermatozoa and in the reproductive tract of the male rat. Biol. Reprod. 45: 195–207.

    PubMed  CAS  Google Scholar 

  • Tobe, T., Minoshima, S., Yamase, S., Choi, N.H., Tomita, M., Shimizu, N., Purrello, M., Bettuzzi, S., Di Pietro, C., Mirabile, E., Di Blasi, M., Rimini, R., Grzeschik, K.H., Ingletti, C., Corti, A., Sichel, G., Wong, P., Taillefer, D., Lakins, J., Pineault, J., Chader, G., and Tenniswood, M., 1991, Assignment of a human serum glycoprotein SP-40,40 gene (CLI) to chromosome 8. Cytogenet. Cell Genet. 57: 193–195.

    PubMed  CAS  Google Scholar 

  • Trougakos, I.P., and Gonos, E.S., 2002, Clusterin/apolipoprotein J in human aging and cancer. Int. J. Biochem. Cell Biol. 34: 1430–1448.

    PubMed  CAS  Google Scholar 

  • Trougakos, I.P., So, A., Jansen, B., Gleave, M.E., and Gonos, E.S., 2004, Silencing expression of the clusterin/apolipoprotein J gene in human cancer cells using small interfering RNA induces spontaneous apoptosis, reduced growth ability, and cell sensitization to genotoxic and oxidative stress. Cancer Res. 64: 1834–1842.

    PubMed  CAS  Google Scholar 

  • Urban, J., Parczyk, K., Leutz, A., Kayne, M., and Kondor-Koch, C., 1987, Constitutive apical secretion of an 80-kD sulfated glycoprotein complex in the polarized epithelial Madin-Darby canine kidney cell line. J. Cell. Biol. 105: 2735–2743.

    PubMed  CAS  Google Scholar 

  • Urmoneit, B., Prikulis, I., Wihl, G., D’Urso, D., Frank, R., Heeren, J., Beisiegel, U., and Prior, R., 1997, Cerebrovascular smooth muscle cells internalize Alzheimer amyloid beta protein via a lipoprotein pathway: implications for cerebral amyloid angiopathy. Lab. Invest. 77: 157–166.

    PubMed  CAS  Google Scholar 

  • Viard, I., Wehrli, P., Jornot, L., Bullani, R., Vechietti, J.L., Schifferli, J.A., Tschopp, J., and French, L.E., 1999, Clusterin gene expression mediates resistance to apoptotic cell death induced by heat shock and oxidative stress. J. Invest. Dermatol. 112: 290–296.

    PubMed  CAS  Google Scholar 

  • Wilson, M.R., and Easterbrook-Smith, S.B., 2000, Clusterin is a secreted mammalian chaperone. Trends Biochem. Sci. 25: 95–98.

    PubMed  CAS  Google Scholar 

  • Witte, D.P., Aronow, B.J., Stauderman, M.L., Stuart, W.D., Clay, M.A., Gruppo, R.A., Jenkins, S.H., and Harmony, J.A., 1993, Platelet activation releases megakaryocyte-synthesized apolipoprotein J, a highly abundant protein in atheromatous lesions. Am. J. Pathol. 143: 763–773.

    PubMed  CAS  Google Scholar 

  • Wong, P., Taillefer, D., Lakins, J., Pineault, J., Chader, G., and Tenniswood, M., 1994, Molecular characterization of human TRPM-2/clusterin, a gene associated with sperm maturation, apoptosis and neurodegeneration. Eur. J. Biochem. 221: 917–925.

    PubMed  CAS  Google Scholar 

  • Yan, S.D., Chen, X., Fu, J., Chen, M., Zhu, H., Roher, A., Slattery, T., Zhao, L., Nagashima, M., Morser, J., Migheli, A., Nawroth, P., Stern, D., and Schmidt, A.M., 1996, RAGE and amyloid-beta peptide neurotoxicity in Alzheimer’s disease. Nature 382: 685–691.

    PubMed  CAS  Google Scholar 

  • Yang, C.R., Leskov, K., Hosley-Eberlein, K., Criswell, T., Pink, J.J., Kinsella, T.J., and Boothman, D.A., 2000, Nuclear clusterin/XIP8, an x-ray-induced Ku70-binding protein that signals cell death. Proc. Natl. Acad. Sci. USA 97: 5907–5912.

    PubMed  CAS  Google Scholar 

  • Yasuhara, O., Aimi, Y., and McGeer, P.L., 1994, Expression of the complement membrane attack complex and its inhibitors in Pick disease brain. Brain Res. 652: 346–349.

    PubMed  CAS  Google Scholar 

  • Zlokovic, B.V., Mattel, C.L., Matsubara, E., McComb, J.G., Zheng, G., McCluskey, R.T., Frangione, B., and Ghiso, J., 1996, Glycoprotein 330/megalin: probable role in receptor-mediated transport of apolipoprotein J alone and in a complex with Alzheimer disease amyloid beta at the blood-brain and blood-cerebrospinal fluid barriers. Proc. Natl. Acad. Sci. USA 93: 4229–4234.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centro National de Microbiología, Instituto de Salud Carlos III, 28220, Majadahonda, Madrid, Spain

    Miguel Calero

  2. Department of Pathology, New York University School of Medicine, New York, NY, 10016, USA

    Miguel Calero, Agueda Rostagno, Blas Frangione & Jorge Ghiso

Authors
  1. Miguel Calero
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Agueda Rostagno
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Blas Frangione
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jorge Ghiso
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute of Zoology, University of Mainz, Mainz, Germany

    J. Robin Harris

  2. Institute of Biochemistry, University of Mainz, Mainz, Germany

    Falk Fahrenholz

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer Science+Business Media, Inc.

About this chapter

Cite this chapter

Calero, M., Rostagno, A., Frangione, B., Ghiso, J. (2005). Clusterin and Alzheimer’s Disease. In: Harris, J.R., Fahrenholz, F. (eds) Alzheimer’s Disease. Subcellular Biochemistry, vol 38. Springer, Boston, MA . https://doi.org/10.1007/0-387-23226-5_14

Download citation

Publish with us

Policies and ethics

Search

Navigation