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The Double-Edged Flower: Roles of Complement Protein C1q in Neurodegenerative Diseases

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Current Topics in Complement

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8. References

  1. L.E. Hebert, P.A. Scherr, J.L. Bienias, D.A. Bennett, and D.A. Evans, Alzheimer’s disease in the US population: prevalence estimates using the 2000 census, Arch Neurol 60, 1119–1122 (2003).

    Article  PubMed  Google Scholar 

  2. T.E. Golde, The Abeta hypothesis: leading us to rationally-designed therapeutic strategies for the treatment or prevention of Alzheimer disease, Brain Pathol 15, 84–87 (2005).

    Article  PubMed  CAS  Google Scholar 

  3. R.E. Tanzi and L. Bertram, Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective, Cell 120, 545–555 (2005).

    Article  PubMed  CAS  Google Scholar 

  4. D.M. Walsh, I. Klyubin, J.V. Fadeeva, W.K. Cullen, R. Anwyl, M.S. Wolfe, M.J. Rowan, and D.J. Selkoe, Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo, Nature 416, 535–539 (2002).

    Article  PubMed  CAS  Google Scholar 

  5. R.H. Takahashi, T.A. Milner, F. Li, E.E. Nam, M.A. Edgar, H. Yamaguchi, M.F. Beal, H. Xu, P. Greengard, and G.K. Gouras, Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology, Am J Pathol 161, 1869–1879 (2002).

    PubMed  CAS  Google Scholar 

  6. M. Koistinaho, M. Ort, J.M. Cimadevilla, R. Vondrous, B. Cordell, J. Koistinaho, J. Bures, and L.S. Higgins, Specific spatial learning deficits become severe with age in beta-amyloid precursor protein transgenic mice that harbor diffuse beta-amyloid deposits but do not form plaques, Proc Natl Acad Sci USA 98, 14675–14680 (2001).

    Article  PubMed  CAS  Google Scholar 

  7. S. Oddo, A. Caccamo, J.D. Shepherd, M.P. Murphy, T.E. Golde, R. Kayed, R. Metherate, M.P. Mattson, Y. Akbari, and F.M. LaFerla, Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction, Neuron 39, 409–421 (2003).

    Article  PubMed  CAS  Google Scholar 

  8. M.A. Westerman, D. Cooper-Blacketer, A. Mariash, L. Kotilinek, T. Kawarabayashi, L.H. Younkin, G.A. Carlson, S.G. Younkin, and K.H. Ashe, The relationship between Abeta and memory in the Tg2576 mouse model of Alzheimer’s disease, J Neurosci 22, 1858–1867 (2002).

    PubMed  CAS  Google Scholar 

  9. Y. Gong, L. Chang, K.L. Viola, P.N. Lacor, M.P. Lambert, C.E. Finch, G.A. Krafft, and W.L. Klein, Alzheimer’s disease-affected brain: presence of oligomeric A beta ligands (ADDLs) suggests a molecular basis for reversible memory loss, Proc Natl Acad Sci USA 100, 10417–10422 (2003).

    Article  PubMed  CAS  Google Scholar 

  10. R. Kayed, E. Head, J.L. Thompson, T.M. McIntire, S.C. Milton, C.W. Cotman, and C.G. Glabe, Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis, Science 300, 486–489 (2003).

    Article  PubMed  CAS  Google Scholar 

  11. B. Urbanc, L. Cruz, R. Le, J. Sanders, K.H. Ashe, K. Duff, H.E. Stanley, M.C. Irizarry, and B.T. Hyman, Neurotoxic effects of thioflavin S-positive amyloid deposits in transgenic mice and Alzheimer’s disease, Proc Natl Acad Sci USA 99, 13990–13995 (2002).

    Article  PubMed  CAS  Google Scholar 

  12. H. Akiyama, S. Barger, S. Barnum, B. Bradt, J. Bauer, G.M. Cole, N.R. Cooper, P. Eikelenboom, M. Emmerling, B.L. Fiebich, C.E. Finch, S. Frautschy, W.S. Griffin, H. Hampel, M. Hull, G. Landreth, L. Lue, R. Mrak, I.R. Mackenzie, P.L. McGeer, M.K. O’Banion, J. Pachter, G. Pasinetti, C. Plata-Salaman, J. Rogers, R. Rydel, Y. Shen, W. Streit, R. Strohmeyer, I. Tooyoma, F.L. Van Muiswinkel, R. Veerhuis, D. Walker, S. Webster, B. Wegrzyniak, G. Wenk, and T. Wyss-Coray, Inflammation and Alzheimer’s disease, Neurobiol Aging 21, 383–421 (2000).

    Article  PubMed  CAS  Google Scholar 

  13. R.L. Cotter, W.J. Burke, V.S. Thomas, J.F. Potter, J.L. Zheng, and H.E. Gendelman, Insights into the neurodegenerative process of Alzheimer’s disease: a role for mononuclear phagocyte-associated inflammation and neurotoxicity, J Leuk Biol 65, 416–27 (1999).

    CAS  Google Scholar 

  14. B.J. Cummings, E. Head, A.J. Afagh, N.W. Milgram, and C.W. Cotman, Beta-amyloid accumulation correlates with cognitive dysfunction in the aged canine., Neurobiol Learning Memory 66, 11–23 (1996).

    Article  CAS  Google Scholar 

  15. B.J. Cummings, C.J. Pike, R. Shankle, and C.W. Cotman, Beta-amyloid deposition and other measures of neuropathology predict cognitive status in Alzheimer’s disease [see comments], Neurobiol Aging 17, 921–933 (1996).

    Article  PubMed  CAS  Google Scholar 

  16. D.A. Bobak, T.G. Gaither, M.M. Frank, and A.J. Tenner, Modulation of FcR function by complement: subcomponent C1q enhances the phagocytosis of IgG-opsonized targets by human monocytes and culture-derived macrophages, J Immunol 138, 1150–1156 (1987).

    PubMed  CAS  Google Scholar 

  17. P.R. Taylor, A. Carugati, V.A. Fadok, H.T. Cook, M. Andrews, M.C. Carroll, J.S. Savill, P.M. Henson, M. Botto, and M.J. Walport, A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo, J Exp Med 192, 359–366 (2000).

    Article  PubMed  CAS  Google Scholar 

  18. A. Sahu and J.D. Lambris, Structure and biology of complement protein C3, a connecting link between innate and acquired immunity, Immunol Rev 180, 35–48 (2001).

    Article  PubMed  CAS  Google Scholar 

  19. C1q in Alzheimer’s disease brain, Exp Neurol 138, 22–32 (1996).

    Google Scholar 

  20. R. Strohmeyer, Y. Shen, and J. Rogers, Detection of complement alternative pathway mRNA and proteins in Alzheimer’s disease brain., Mol Brain Res 81, 7–18 (2000).

    Article  PubMed  CAS  Google Scholar 

  21. H. Zanjani, C.E. Finch, C. Kemper, J. Atkinson, D. McKeel, J.C. Morris, and J.L. Price, Complement activation in very early Alzheimer disease, Alz Dis Assoc Disorders 19, 55–66 (2005).

    Article  CAS  Google Scholar 

  22. P. Eikelenboom, C.E. Hack, J.M. Rozemuller, and F.C. Stam, Complement activation in amyloid plaques in Alzheimer’s dementia, Virch Arch B Cell Pathol 56, 259–262 (1989).

    CAS  Google Scholar 

  23. P.L. McGeer, H. Akiyama, S. Itagaki, and E.G. McGeer, Immune system response in Alzheimer’s disease, Can J Neurol Sci 16, 516–527 (1989).

    PubMed  CAS  Google Scholar 

  24. Y. Shen, L. Lue, L. Yang, A. Roher, Y. Kuo, R. Strohmeyer, W.J. Goux, V. Lee, G.V. Johnson, S.D. Webster, N.R. Cooper, B. Bradt, and J. Rogers, Complement activation by neurofibrillary tangles in Alzheimer’s disease, Neurosci Lett 305, 165–168 (2001).

    Article  PubMed  CAS  Google Scholar 

  25. S.A. Johnson, M. Lampert-Etchells, G.M. Pasinetti, I. Rozovsky, and C. Finch, Complement mRNA in the mammalian brain: Responses to Alzheimer’s disease and experimental brain lesioning, Neurobiol Aging 13, 641–648 (1992).

    Article  PubMed  CAS  Google Scholar 

  26. Y. Shen, R. Li, E.G. McGeer, and P.L. McGeer, Neuronal expression of mRNAs for complement proteins of the classical pathway in Alzheimer’s brain, Brain Res 769, 391–395 (1997).

    Article  PubMed  CAS  Google Scholar 

  27. S. Nataf, P.F. Stahel, N. Davoust, and S.R. Barnum, Complement anaphylatoxin receptors on neurons: new tricks for old receptors? Trends Neurosci 22, 397–402 (1999).

    Article  PubMed  CAS  Google Scholar 

  28. S. Webster, L.F. Lue, L. Brachova, A.J. Tenner, P.L. McGeer, K. Terai, D.G. Walker, B. Bradt, N.R. Cooper, and J. Rogers, Molecular and cellular characterization of the membrane attack complex, C5b-9, in Alzheimer’s disease, Neurobiol Aging 18, 415–421 (1997).

    Article  PubMed  CAS  Google Scholar 

  29. E. Head, B.Y. Azizeh, I.T. Lott, A.J. Tenner, C.W. Cotman, and D.H. Cribbs, Complement association with neurons and β-amyloid deposition in the brains of aged individuals with Down syndrome, Neurobiol Dis 8, 252–265 (2001).

    Article  PubMed  CAS  Google Scholar 

  30. M.I. Fonseca, C.H. Kawas, J.C. Troncoso, and A.J. Tenner, Neuronal localization of C1q in preclinical Alzheimer’s disease, Neurobiol Dis 15, 40–46 (2004).

    Article  PubMed  CAS  Google Scholar 

  31. S.E. Stoltzner, T.J. Grenfell, C. Mori, K.E. Wisniewski, T.M. Wisniewski, D.J. Selkoe, and C.A. Lemere, Temporal accrual of complement proteins in amyloid plaques in Down’s syndrome with Alzheimer’s disease, Am J Pathol 156, 489–499 (2000).

    PubMed  CAS  Google Scholar 

  32. J. Rogers, N.R. Cooper, S. Webster, J. Schultz, P.L. McGeer, S.D. Styren, W.H. Civin, L. Brachova, B. Bradt, P. Ward, and I. Lieberburg, Complement activation by beta-amyloid in Alzheimer disease., Proc Natl Acad Sci USA 89, 10016–10020 (1992).

    Article  PubMed  CAS  Google Scholar 

  33. H. Jiang, D. Burdick, C.G. Glabe, C.W. Cotman, and A.J. Tenner, β-amyloid activates complement by binding to a specific region of the collagen-like domain of the C1q A chain, J Immunol 152, 5050–5059 (1994).

    PubMed  CAS  Google Scholar 

  34. S. Chen, R.C. Frederickson, and K.R. Brunden, Neuroglial-mediated immunoin-flammatory responses in Alzheimer’s disease: complement activation and therapeutic approaches, Neurobiol Aging 17, 781–787 (1996).

    Article  PubMed  CAS  Google Scholar 

  35. B.M. Bradt, W.P. Kolb, and N.R. Cooper, Complement-dependent proinflammatory properties of the Alzheimer’s disease β-peptide, J Exp Med 188, 431–438 (1998).

    Article  PubMed  CAS  Google Scholar 

  36. M.D. Watson, A.E. Roher, K.S. Kim, K. Spiegel, and M.R. Emmerling, Complement interactions with amyloid-β1-42: a nidus for inflammation in AD brains., Amyloid: Int J Exp Clin Invest 4, 147–156 (1997).

    CAS  Google Scholar 

  37. P. Velazquez, D.H. Cribbs, T.L. Poulos, and A.J. Tenner, Aspartate residue 7 in amyloid β-protein is critical for classical complement pathway activation: Implications for Alzheimer’s disease pathogenesis, Nature Med 3, 77–79 (1997).

    Article  PubMed  CAS  Google Scholar 

  38. S. Webster, B. Bradt, J. Rogers, and N.R. Cooper, Aggregation state-dependent activation of the classical complement pathway by the amyloid beta peptide, J Neurochem 69, 388–398 (1997).

    Article  PubMed  CAS  Google Scholar 

  39. D.H. Cribbs, P. Velazquez, B. Soreghan, C.G. Glabe, and A.J. Tenner, Complement activation by cross-linked truncated and chimeric full-length β-amyloid, NeuroReport 8, 3457–3462 (1997).

    Article  PubMed  CAS  Google Scholar 

  40. S. Webster, C. Glabe, and J. Rogers, Multivalent binding of complement protein C1q to the amyloid β-peptide (Aβ) promotes the nucleation phase of Aβ aggregation, Biochem Biophys Res Commun 217, 869–875 (1995).

    Article  PubMed  CAS  Google Scholar 

  41. P. Tacnet-Delorme, S. Chevallier, and G.J. Arlaud, Beta-amyloid fibrils activate the C1 complex of complement under physiological conditions: evidence for a binding site for A beta on the C1q globular regions, J Immunol 167, 6374–6381 (2001).

    PubMed  CAS  Google Scholar 

  42. C. Gaboriaud, J. Juanhuix, A. Gruez, M. Lacroix, C. Darnault, D. Pignol, D. Verger, J.C. Fontecilla-Camps, and G.J. Arlaud, The crystal structure of the globular head of complement protein C1q provides a basis for its versatile recognition properties, J Biol Chem 278, 46974–46982 (2003).

    Article  PubMed  CAS  Google Scholar 

  43. J. Yao, L. Harvath, D.L. Gilbert, and C.A. Colton, Chemotaxis by a CNS macrophage, the microglia, J Neurosci Res 27, 36–42 (1990).

    Article  PubMed  CAS  Google Scholar 

  44. A.J. Tenner and S.D. Webster. “Complement-mediated injury and inflammation in the pathogenesis of Alzheimer’s Disease.” In Inflammatory events in neurodegeneration, eds., S.C. Bondy and A. Campbell, pp. 119–138. Scottsdale, AZ: Prominent Press (2001).

    Google Scholar 

  45. A.J. Tenner, Complement in Alzheimer’s disease: opportunities for modulating protective and pathogenic events, Neurobiol Aging 22, 849–861 (2001).

    Article  PubMed  CAS  Google Scholar 

  46. K. Yasojima, E.G. McGeer, and P.L. McGeer, Complement regulators C1 inhibitor and CD59 do not significantly inhibit complement activation in Alzheimer disease, Brain Res 833, 297–301 (1999).

    Article  PubMed  CAS  Google Scholar 

  47. C. Sturchler-Pierrat, D. Abramowski, M. Duke, K.H. Wiederhold, C. Mistl, S. Rothacher, B. Ledermann, K. Burki, P. Frey, P.A. Paganetti, C. Waridel, M.E. Calhoun, M. Jucker, A. Probst, M. Staufenbiel, and B. Sommer, Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology, Proc Natl Acad Sci USA 94, 13287–13292 (1997).

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  49. K.K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, and G. Cole, Correlative memory deficits, Aβ elevations, and amyloid plaques in transgenic mice, Science 274, 99–102 (1996).

    Article  PubMed  CAS  Google Scholar 

  50. D. Morgan, Learning and memory deficits in APP transgenic mouse models of amyloid deposition, Neurochem Res 28, 1029–1034 (2003).

    Article  PubMed  CAS  Google Scholar 

  51. S.A. Frautschy, F.S. Yang, M. Irrizarry, B. Hyman, T.C. Saido, K. Hsiao, and G.M. Cole, Microglial response to amyloid plaques in APPsw transgenic mice, Am J Pathol 152, 307–317 (1998).

    PubMed  CAS  Google Scholar 

  52. L. Holcomb, M.N. Gordon, E. McGowan, X. Yu, S. Benkovic, P. Jantzen, K. Wright, I. Saad, R. Mueller, D. Morgan, S. Sanders, C. Zehr, K. O’Campo, J. Hardy, C.M. Prada, C. Eckman, S. Younkin, K. Hsiao, and K. Duff, Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes, Nat Med 4, 97–100 (1998).

    Article  PubMed  CAS  Google Scholar 

  53. J. Apelt and R. Schliebs, Beta-amyloid-induced glial expression of both pro-and anti-inflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology, Brain Res 894, 21–30 (2001).

    Article  PubMed  CAS  Google Scholar 

  54. Y. Matsuoka, M. Picciano, B. Malester, J. LaFrancois, C. Zehr, J.M. Daeschner, J.A. Olschowka, M.I. Fonseca, M.K. O’Banion, A.J. Tenner, C.A. Lemere, and K. Duff, Inflammatory responses to amyloidosis in a transgenic mouse model of Alzheimer’s disease, Am J Pathol 158, 1345–1354 (2001).

    PubMed  CAS  Google Scholar 

  55. M.C. Irizarry, F. Soriano, M. McNamara, K.J. Page, D. Schenk, D. Games, and B.T. Hyman, Abeta deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse, J Neurosci 17, 7053–7059 (1997).

    PubMed  CAS  Google Scholar 

  56. A. Takeuchi, M.C. Irizarry, K. Duff, T.C. Saido, A.K. Hsiao, M. Hasegawa, D.M. Mann, B.T. Hyman, and T. Iwatsubo, Age-related amyloid beta deposition in transgenic mice overexpressing both Alzheimer mutant presenilin 1 and amyloid beta precursor protein Swedish mutant is not associated with global neuronal loss, Am J Pathol 157, 331–339 (2000).

    PubMed  CAS  Google Scholar 

  57. P. Chapman, G.L. White, M.W. Jones, D. Cooper-Blacketer, V.J. Marshall, M. Irizarry, L. Younkin, M.A. Good, T.V.P. Bliss, B.T. Hyman, S.G. Younkin, and K.K. Hsiao, Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice, Nat Neurosci 2, 271–276 (1999).

    Article  PubMed  CAS  Google Scholar 

  58. M. Botto, C1q knock-out mice for the study of complement deficiency in autoimmune disease, Exp Clin Immunogenet 15, 231–234 (1998).

    Article  PubMed  CAS  Google Scholar 

  59. M. Botto, C. Dell’agnola, A.E. Bygrave, E.M. Thompson, H.T. Cook, F. Petry, M. Loos, P.P. Pandolfi, and M.J. Walport, Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies, Nat Genet 19, 56–59 (1998).

    Article  PubMed  CAS  Google Scholar 

  60. M.I. Fonseca, J. Zhou, M. Botto, and A.J. Tenner, Absence of C1q leads to less neuropathology in transgenic mouse models of Alzheimer’s disease, J Neurosci 24, 6457–6465 (2004).

    Article  PubMed  CAS  Google Scholar 

  61. R.D. Terry, E. Masliah, D.P. Salmon, N. Butters, R. DeTeresa, R. Hill, L.A. Hansen, and R. Katzman, Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment, Ann Neurol 30, 572–580 (1991).

    Article  PubMed  CAS  Google Scholar 

  62. E. Masliah, M. Mallory, L. Hansen, R. DeTeresa, M. Alford, and R. Terry, Synaptic and neuritic alterations during the progression of Alzheimer’s disease, Neurosci Lett 174, 67–72 (1994).

    Article  PubMed  CAS  Google Scholar 

  63. H. Cremer, G. Chazal, A. Carleton, C. Goridis, J.D. Vincent, and P.M. Lledo, Long-term but not short-term plasticity at mossy fiber synapses is impaired in neural cell adhesion molecule-deficient mice, Proc Natl Acad Sci USA 95, 13242–13247 (1998).

    Article  PubMed  CAS  Google Scholar 

  64. V. Ramirez-Amaya, I. Balderas, J. Sandoval, M.L. Escobar, and F. Bermudez-Rattoni, Spatial long-term memory is related to mossy fiber synaptogenesis, J Neurosci 21, 7340–7348 (2001).

    PubMed  CAS  Google Scholar 

  65. D.A. Loeffler, Using animal models to determine the significance of complement activation in Alzheimer’s disease. J Neuroinflam 1, 18 (2004).

    Article  CAS  Google Scholar 

  66. C. Schwab, M. Hosokawa, and P.L. McGeer, Transgenic mice overexpressing amyloid beta protein are an incomplete model of Alzheimer disease, Exp Neurol 188, 52–64 (2004).

    Article  PubMed  CAS  Google Scholar 

  67. G.L. Ong and M.J. Mattes, Mouse strains with typical mammalian levels of complement activity, J Immunol Meth 125, 147–158 (1989).

    Article  CAS  Google Scholar 

  68. R.O. Ebanks and D.E. Isenman, Mouse complement component C4 is devoid of classical pathway C5 convertase subunit activity, Mol Immunol 33, 297–309 (1996).

    Article  PubMed  CAS  Google Scholar 

  69. A.H. Moore and M.K. O’Banion, Neuroinflammation and anti-inflammatory therapy for Alzheimer’s disease, Adv Drug Del Rev 54, 1627–1656 (2002).

    Article  CAS  Google Scholar 

  70. C.A. Lemere, E.T. Spooner, J.F. Leverone, C. Mori, M. Iglesias, J.K. Bloom, and T.J. Seabrook, Amyloid-beta immunization in Alzheimer’s disease transgenic mouse models and wildtype mice, Neurochem Res 28, 1017–1027 (2003).

    Article  PubMed  CAS  Google Scholar 

  71. D.J. Selkoe and D. Schenk, Alzheimer’s disease: molecular understanding predicts amyloid-based therapeutics, Annu Rev Pharmacol Toxicol 43, 545–584 (2003).

    Article  PubMed  CAS  Google Scholar 

  72. R.J. Mead, S.K. Singhrao, J.W. Neal, H. Lassmann, and B.P. Morgan, The membrane attack complex of complement causes severe demyelination associated with acute axonal injury, J Immunol 168, 458–465 (2002).

    PubMed  CAS  Google Scholar 

  73. C. Schwab and P.L. McGeer, Complement activated C4d immunoreactive oligodendrocytes delineate small cortical plaques in multiple sclerosis, Exp Neurol 174, 81–88 (2002).

    Article  PubMed  CAS  Google Scholar 

  74. P. Gasque, Y.D. Dean, E.P. McGreal, J. VanBeek, and B.P. Morgan, Complement components of the innate immune system in health and disease in the CNS, Immunopharmacology 49, 171–186 (2000).

    Article  PubMed  CAS  Google Scholar 

  75. M.L. Shin, H. Rus, and F. Niculescu. Complement system in central nervous system disorders. In The human complement system in health and disease, eds. J.E. Volanakis and M.M. Frank, pp. 499–525. New York: Marcel Dekker Inc., 1998.

    Google Scholar 

  76. K.D. Whitney and J.O. McNamara, GluR3 autoantibodies destroy neural cells in a complement-dependent manner modulated by complement regulatory proteins, J. Neurosci 20, 7307–7316 (2000).

    PubMed  CAS  Google Scholar 

  77. A. Rostagno, T. Revesz, T. Lashley, Y. Tomidokoro, L. Magnotti, H. Braendgaard, G. Plant, M. Bojsen-Moller, J. Holton, B. Frangione, and J. Ghiso, Complement activation in chromosome 13 dementias: similarities with Alzheimer’s disease, J Biol. Chem 277, 49782–49790 (2002).

    Article  PubMed  CAS  Google Scholar 

  78. L.V. Johnson, W.P. Leitner, A.J. Rivest, M.K. Staples, M.J. Radeke, and D.H. Anderson, The Alzheimer’s Aβ-peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration, Proc Natl Acad Sci USA (2002).

    Google Scholar 

  79. P. Eikelenboom, C. Bate, W.A. van Gool, J.J. Hoozemans, J.M. Rozemuller, R. Veerhuis, and A. Williams, Neuroinflammation in Alzheimer’s disease and prion disease, Glia 40, 232–439 (2002).

    Article  PubMed  CAS  Google Scholar 

  80. L. Liu, H. Aldskogius, and M. Svensson, Ultrastructural localization of immunoglobulin G and complement C9 in the brain stem and spinal cord following peripheral nerve injury: an immunoelectron microscopic study, J Neurocytol 27, 737–748 (1998).

    Article  PubMed  CAS  Google Scholar 

  81. T. Watanabe, T. Yamamoto, Y. Abe, N. Saito, T. Kumagai, and H. Kayama, Differential activation of microglia after experimental spinal cord injury, J Neurotrauma 16, 255–265 (1999).

    Article  PubMed  CAS  Google Scholar 

  82. G.S. Hageman, D.H. Anderson, L.V. Johnson, L.S. Hancox, A.J. Taiber, L.I. Hardisty, J.L. Hageman, H.A. Stockman, J.D. Borchardt, K.M. Gehrs, R.J. Smith, G. Silvestri, S.R. Russell, C.C. Klaver, I. Barbazetto, S. Chang, L.A. Yannuzzi, G.R. Barile, J.C. Merriam, R.T. Smith, A.K. Olsh, J. Bergeron, J. Zernant, J.E. Merriam, B. Gold, M. Dean, and R. Allikmets, A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration, Proc Natl Acad Sci USA 102, 7227–7232 (2005).

    Article  PubMed  CAS  Google Scholar 

  83. R.J. Klein, C. Zeiss, E.Y. Chew, J.Y. Tsai, R.S. Sackler, C. Haynes, A.K. Henning, J.P. Sangiovanni, S.M. Mane, S.T. Mayne, M.B. Bracken, F.L. Ferris, J. Ott, C. Barnstable, and J. Hoh, Complement factor H polymorphism in age-related macular degeneration, Science (2005).

    Google Scholar 

  84. A.O. Edwards, I.R. Ritter, K.J. Abel, A. Manning, C. Panhuysen, and L.A. Farrer, Complement factor H polymorphism and age-related macular degeneration, Science (2005).

    Google Scholar 

  85. J.L. Haines, M.A. Hauser, S. Schmidt, W.K. Scott, L.M. Olson, P. Gallins, K.L. Spencer, S.Y. Kwan, M. Noureddine, J.R. Gilbert, N. Schnetz-Boutaud, A. Agarwal, E.A. Postel, and M.A. Pericak-Vance, Complement factor H variant increases the risk of age-related macular degeneration, Science (2005).

    Google Scholar 

  86. T. Wyss-Coray, F. Yan, A.H. Lin, J.D. Lambris, J.J. Alexander, R.J. Quigg, and E. Masliah, Prominent neurodegeneration and increased plaque formation in complement-inhibited Alzheimer’s mice, Proc Natl Acad Sci USA 99, 10837–10842 (2002).

    Article  PubMed  CAS  Google Scholar 

  87. G.M. Pasinetti, G. Tocco, S. Sakhi, W.D. Musleh, M.G. DeSimoni, P. Mascarucci, S. Schreiber, M. Baudry, and C.E. Finch, Hereditary deficiencies in complement C5 are associated with intensified neurodegenerative responses that implicate new roles for the C-system in neuronal and astrocytic functions, Neurobiol Dis 3, 197–204 (1996).

    Article  PubMed  CAS  Google Scholar 

  88. S.A. O’Barr, J. Caguioa, D. Gruol, G. Perkins, J.A. Ember, T. Hugli, and N.R. Cooper, Neuronal expression of a functional receptor for the C5a complement activation fragment, J Immunol 166, 4154–4162 (2001).

    PubMed  CAS  Google Scholar 

  89. J. Daly and G.J. Kotwal, Proinflammatory complement activation by the Aβ peptide of Alzheimer’s disease is biologically significant and can be blocked by Vaccinia virus complement control protein, Neurobiol Aging 19, 619–627 (1998).

    Article  PubMed  CAS  Google Scholar 

  90. G. Tocco, W. Musleh, S. Sakhi, S.S. Schreiber, M. Baudry, and G.M. Pasinetti, Complement and glutamate neurotoxicity: genotypic influences of C5 in a mouse model of hippocampal neurodegeneration, Mol Chem Neuropathol 31, 289–300 (1997).

    PubMed  CAS  Google Scholar 

  91. S. Okinaga, D. Slattery, A. Humbles, Z. Zsengeller, O. Morteau, M.B. Kinrade, R.M. Brodbeck, J.E. Krause, H.R. Choe, N.P. Gerard, and C. Gerard, C5L2, a nonsignaling C5A binding protein, Biochemistry 42, 9406–9415 (2003).

    Article  PubMed  CAS  Google Scholar 

  92. S.K. Singhrao, J.W. Neal, B.P. Morgan, and P. Gasque, Increased complement biosynthesis by microglia and complement activation on neurons in Huntington’s disease, Exp Neurol 159, 362–376 (1999).

    Article  PubMed  CAS  Google Scholar 

  93. B. Dietzschold, W. Schwaeble, M.K.H. Schäfer, D.C. Hooper, Y.M. Zehng, F. Petry, H. Sheng, T. Fink, M. Loos, H. Koprowski, and E. Weihe, Expression of C1q, a subcomponent of the rat complement system, is dramatically enhanced in brains of rats with either Borna disease or experimental allergic encephalomyelitis, J Neurol Sci 130, 11–16 (1995).

    Article  PubMed  CAS  Google Scholar 

  94. S.K. Goldsmith, P. Wals, I. Rozovsky, T.E. Morgan, and C.E. Finch, Kainic acid and decorticating lesions stimulate the synthesis of C1q protein in adult rat brain, J. Neurochem 68, 2046–2052 (1997).

    Article  PubMed  CAS  Google Scholar 

  95. L. Spielman, D. Winger, L. Ho, P.S. Aisen, E. Shohami, and M. Pasinetti, Induction of the complement component C1qB in brain of transgenic mice with neuronal overexpression of human cyclooxygenase-2, Acta Neuropathol (Berl) 103, 157–162 (2002).

    Article  CAS  Google Scholar 

  96. B.M. Bellander, S.K. Singhrao, M. Ohlsson, P. Mattsson, and M. Svensson, Complement activation in the human brain after traumatic head injury, J Neurotrauma 18, 1295–1311 (2001).

    Article  PubMed  CAS  Google Scholar 

  97. C.K. Lee, R. Weindruch, and T.A. Prolla, Gene-expression profile of the ageing brain in mice, Nat Genet 25, 294–297 (2000).

    Article  PubMed  CAS  Google Scholar 

  98. B.A. Bahr, K.B. Hoffman, A.J. Yang, U.S. Hess, C.G. Glabe, and G. Lynch, Amyloid β protein is internalized selectively by hippocampal field CA1 and causes neu rons to accumulate amyloidogenic carboxyterminal fragments of the amyloid precursor protein, J Comp Neurol 397, 139–147 (1998).

    Article  PubMed  CAS  Google Scholar 

  99. R. Fan and A.J. Tenner, Complement C1q expression induced by Abeta in rat hippocampal organotypic slice cultures, Exp Neurol 185, 241–253 (2004).

    Article  PubMed  CAS  Google Scholar 

  100. R. Fan and A.J. Tenner, Differential regulation of Abeta42-induced neuronal C1q synthesis and microglial activation, J Neuroinflam. 2, 1 (2005).

    Article  CAS  Google Scholar 

  101. F. Dandoy-Dron, F. Guillo, L. Benboudjema, J.P. Deslys, C. Lasmezas, D. Dormont, M.G. Tovey, and M. Dron, Gene expression in scrapie: cloning of a new scrapie-responsive gene and the identification of increased levels of seven other mRNA transcripts, J Biol Chem 273, 7691–7697 (1998).

    Article  PubMed  CAS  Google Scholar 

  102. M. Lampert-Etchells, G.M. Pasinetti, C.E. Finch, and S.A. Johnson, Regional localization of cells containing complement C1q and C4 mRNAs in the frontal cortex during Alzheimer’s disease, Neurodegeneration 2, 111–121 (1993).

    Google Scholar 

  103. J. Huang, L.J. Kim, R. Mealey Jr., H.C. Marsh, Y. Zhang, A.J. Tenner, E.S. Connolly Jr., and D.J. Pinsky, Neuronal protection in stroke by an sLex-glycosylated complement inhibitory protein, Science 285, 595–599 (1999).

    Article  PubMed  CAS  Google Scholar 

  104. K. Terai, D.G. Walker, E.G. McGeer, and P.L. McGeer, Neurons express proteins of the classical complement pathway in Alzheimer disease, Brain Res 769, 385–390 (1997).

    Article  PubMed  CAS  Google Scholar 

  105. K. Yasojima, C. Schwab, E.G. McGeer, and P.L. McGeer, Up-regulated production and activation of the complement system in Alzheimer’s disease brain, Am J Pathol 154, 927–936 (1999).

    PubMed  CAS  Google Scholar 

  106. K. Ohmi, D.S. Greenberg, K.S. Rajavel, S. Ryazantsev, H.H. Li, and E.F. Neufeld, Activated microglia in cortex of mouse models of mucopolysaccharidoses I and IIIB, Proc Natl Acad Sci USA 100, 1902–1907 (2003).

    Article  PubMed  CAS  Google Scholar 

  107. A. Reboul, M.H. Prandini, J.C. Bensa, and M.G. Colomb, Characterization of C1q, C1s and C1 Inh synthesized by stimulated human monocytes in vitro, FEBS Lett 190, 65–68 (1985).

    Article  PubMed  CAS  Google Scholar 

  108. S.D. Webster, M.D. Galvan, E. Ferran, W. Garzon-Rodriguez, C.G. Glabe, and A.J. Tenner, Antibody-mediated phagocytosis of the amyloid β-peptide in microglia is differentially modulated by C1q, J Immunol 166, 7496–7503 (2001).

    PubMed  CAS  Google Scholar 

  109. S.S. Bohlson, M. Zhang, C.E. Ortiz, and A.J. Tenner, CD93 interacts with the PDZ domain-containing adaptor protein GIPC: implications in the modulation of phagocytosis, J Leukoc Biol 77, 80–89 (2005).

    PubMed  CAS  Google Scholar 

  110. C.A. Ogden, A. deCathelineau, P.R. Hoffmann, D. Bratton, B. Ghebrehiwet, V.A. Fadok, and P.M. Henson, C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells, J Exp Med 194, 781–796 (2001).

    Article  PubMed  CAS  Google Scholar 

  111. L.C. Korb and J.M. Ahearn, C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes: complement deficiency and systemic lupus erythematosus revisited, J Immunol 158, 4525–4528 (1997).

    PubMed  CAS  Google Scholar 

  112. J.S. Navratil, S.C. Watkins, J.J. Wisnieski, and J.M. Ahearn, The globular heads of C1q specifically recognize surface blebs of apoptotic vascular endothelial cells, J. Immunol 166, 3231–3239 (2001).

    PubMed  CAS  Google Scholar 

  113. A.J. Nauta, A. Roos, and M.R. Daha, A regulatory role for complement in innate immunity and autoimmunity, Int Arch Allergy Immunol 134, 310–323 (2004).

    Article  PubMed  CAS  Google Scholar 

  114. M. Botto and M.J. Walport, C1q, autoimmunity and apoptosis, Immunobiology 205, 395–406 (2002).

    Article  PubMed  CAS  Google Scholar 

  115. D.A. Mitchell, M.C. Pickering, J. Warren, L. Fossati-Jimack, J. Cortes-Hernandez, H.T. Cook, M. Botto, and M.J. Walport, C1q deficiency and autoimmunity: the effects of genetic background on disease expression, J Immunol 168, 2538–2543 (2002).

    PubMed  CAS  Google Scholar 

  116. Y. Miura-Shimura, K. Nakamura, M. Ohtsuji, H. Tomita, Y. Jiang, M. Abe, D. Zhang, Y. Hamano, H. Tsuda, H. Hashimoto, H. Nishimura, S. Taki, T. Shirai, and S. Hirose, C1q regulatory region polymorphism down-regulating murine c1q protein levels with linkage to lupus nephritis, J Immunol 169, 1334–1339 (2002).

    PubMed  CAS  Google Scholar 

  117. B.G.J.M. Bolscher, R. van Zwieten, I.M. Kramer, R.S. Weening, A.J. Verhoeven, and D. Roos, A phosphoprotein of Mr 47,000, defective in autosomal chronic granulomatous disease, copurifies with one of two soluble components required for NADPH:02 oxidoreductase activity in human neutrophils, J Clin Invest 83, 757–763 (1989).

    Article  PubMed  CAS  Google Scholar 

  118. R.J. Quigg, Y. Kozono, D. Berthiaume, A. Lim, D.J. Salant, A. Weinfeld, P. Griffin, E. Kremmer, and V.M. Holers, Blockade of antibody-induced glomerulonephritis with Crry-Ig, a soluble murine complement inhibitor, J Immunol 160, 4553–4560 (1998).

    PubMed  CAS  Google Scholar 

  119. H.F. Weisman, T. Bartow, M.K. Leppo Jr., H.C. Marsh, G.R. Carson, M.F. Concino, M.P. Boyle, K.H. Roux, M.L. Weisfeldt, and D.T. Fearon, Soluble human complement receptor type 1: in vivo inhibitor of complement suppressing postischemic myocardial inflammation and necrosis, Science 249, 146–151 (1990).

    Article  PubMed  CAS  Google Scholar 

  120. L. Bergamaschini, E. Rossi, C. Storini, S. Pizzimenti, M. Distaso, C. Perego, A. De Luigi, C. Vergani, and D.S. Grazia, Peripheral treatment with enoxaparin, a low molecular weight heparin, reduces plaques and beta-amyloid accumulation in a mouse model of Alzheimer’s disease, J Neurosci 24, 4181–4186 (2004).

    Article  PubMed  CAS  Google Scholar 

  121. A.M. Soulika, M.M. Khan, T. Hattori, F.W. Bowen, B.A. Richardson, C.E. Hack, A. Sahu, L.H. Edmunds Jr., and J.D. Lambris, Inhibition of heparin/protamine complex-induced complement activation by Compstatin in baboons, Clin Immunol 96, 212–221 (2000).

    Article  PubMed  CAS  Google Scholar 

  122. D. Mastellos, D. Morikis, C. Strey, M.C. Holland, and J.D. Lambris, From atoms to systems: a cross-disciplinary approach to complement-mediated functions, Mol. Immunol 41, 153–164 (2004).

    Article  PubMed  CAS  Google Scholar 

  123. M. Otto, H. Hawlisch, P.N. Monk, M. Muller, A. Klos, C.L. Karp, and J. Kohl, C5a mutants are potent antagonists of the C5a receptor (CD88) and of C5L2: position 69 is the locus that determines agonism or antagonism, J Biol Chem 279, 142–151 (2004).

    Article  PubMed  CAS  Google Scholar 

  124. T.M. Woodruff, T.V. Arumugam, I.A. Shiels, R.C. Reid, D.P. Fairlie, and S.M. Taylor, Protective effects of a potent C5a receptor antagonist on experimental acute limb ischemia-reperfusion in rats, J Surg Res 116, 81–90 (2004).

    Article  PubMed  CAS  Google Scholar 

  125. H. Hawlisch, M. Wills-Karp, C.L. Karp, and J. Kohl, The anaphylatoxins bridge innate and adaptive immune responses in allergic asthma, Mol Immunol 41, 123–131 (2004).

    Article  PubMed  CAS  Google Scholar 

  126. D. Spitzer, J. Unsinger, D. Mao, X. Wu, H. Molina, and J.P. Atkinson. ScF-Crry confers resistance against complement-mediated desctruction of Crry deficient RBCs in an in vivo muse model, Mol Immunol 41, 310 (2004).

    Google Scholar 

  127. M. Sarvari, I. Vago, C.S. Weber, J. Nagy, P. Gal, M. Mak, J.P. Kosa, P. Zavodszky, and T. Pazmany, Inhibition of C1q-beta-amyloid binding protects hip pocampal cells against complement mediated toxicity, J Neuroimmunol 137, 12–18 (2003).

    Article  PubMed  CAS  Google Scholar 

  128. C.W. Cotman, A.J. Tenner, and B.J. Cummings, β-amyloid converts an acute phase injury response to chronic injury responses, Neurobiol Aging 17, 723–731 (1996).

    Article  PubMed  CAS  Google Scholar 

  129. E.G. McGeer and P.L. McGeer, Inflammatory processes in Alzheimer’s disease, Prog Neuropsychopharmacol Biol Psychiatry 27, 741–749 (2003).

    Article  PubMed  CAS  Google Scholar 

  130. R. Veerhuis, P. Van der Valk, I. Janssen, S.S. Zhan, W.E. VanNostrand, and P. Eikelenboom, Complement activation in amyloid plaques in Alzheimer’s disease brains does not proceed further than C3, Virchows Arch 426, 603–610 (1995).

    Article  PubMed  CAS  Google Scholar 

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Tenner, A.J., Fonseca, M.I. (2006). The Double-Edged Flower: Roles of Complement Protein C1q in Neurodegenerative Diseases. In: Lambris, J.D. (eds) Current Topics in Complement. Advances in Experimental Medicine and Biology, vol 586. Springer, Boston, MA. https://doi.org/10.1007/0-387-34134-X_11

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