Complement C3 deficiency leads to accelerated amyloid β plaque deposition and neurodegeneration and modulation of the microglia/macrophage phenotype in amyloid precursor protein transgenic mice

Journal of Neuroscience

Volumn 28, Issue 25, 2008, Pages 6333-6341

  Maier, Marcel ^a,d   Peng, Ying ^a   Jiang, Liying ^a   Seabrook, Timothy J ^a   Carroll, Michael C ^b   Lemere, Cynthia A ^a,c  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c Center for Neurologic Diseases   (United States)

^d UNIVERSITY OF ZURICH   (Switzerland)

Author keywords

A peptide; Alzheimer's disease; Amyloid ; C3; Complement; Neurodegeneration

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; AMYLOID PRECURSOR PROTEIN; COMPLEMENT COMPONENT C3;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN HOMOGENATE; CELL DIFFERENTIATION; CONTROLLED STUDY; FRONTAL CORTEX; HIPPOCAMPUS; IMMUNOHISTOCHEMISTRY; MACROPHAGE; MICROGLIA; MOUSE; NERVE DEGENERATION; NONHUMAN; PATHOGENESIS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; ANIMAL; C57BL MOUSE; COMPARATIVE STUDY; GENETICS; HUMAN; METABOLISM; PATHOLOGY; SENILE PLAQUE; TRANSGENIC MOUSE;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; COMPLEMENT C3; HUMANS; MACROPHAGES; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MICROGLIA; NERVE DEGENERATION; PHENOTYPE; SENILE PLAQUES;

EID: 46749087854     PISSN: 02706474     EISSN: 02706474     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.0829-08.2008     Document Type: Article

References (44)

1. Bradt BM, Kolb WP, Cooper NR (1998) Complement-dependent proinflammatory properties of the Alzheimer's disease beta-peptide. J Exp Med 188:431-438.
2. Ehlers MR (2000) CR3: a general purpose adhesion-recognition receptor essential for innate immunity. Microbes Infect 2:289-294.
3. Eikelenboom P, Hack CE, Rozemuller JM, Stam FC (1989) Complement activation in amyloid plaques in Alzheimer's dementia. Virchows Arch B Cell Pathol Incl Mol Pathol 56:259-262.
4. Fonseca MI, Zhou J, Botto M, Tenner AJ (2004) Absence of C1q leads to less neuropathology in transgenic mouse models of Alzheimer's disease. J Neurosci 24:6457-6465.
5. Ford AL, Goodsall AL, Hickey WF, Sedgwick JD (1995) Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting. Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4+ T cells compared. J Immunol 154:4309-4321.
6. Gasque P, Fontaine M, Morgan BP (1995) Complement expression in human brain. Biosynthesis of terminal pathway components and regulators in human glial cells and cell lines. J Immunol 154:4726-4733.
7. Helmy KY, Katschke Jr KJ, Gorgani NN, Kljavin NM, Elliott JM, Diehl L, Scales SJ, Ghilardi N, van Lookeren Campagne M (2006) CRIg: a macrophage complement receptor required for phagocytosis of circulating pathogens. Cell 124:915-927.
8. Irizarry MC, Soriano F, McNamara M, Page KJ, Schenk D, Games D, Hyman BT (1997) Aβ 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.
9. Jin K, Galvan V, Xie L, Mao XO, Gorostiza OF, Bredesen DE, Greenberg DA (2004) Enhanced neurogenesis in Alzheimer's disease transgenic (PDGF-APPSw, Ind) mice. Proc Natl Acad Sci USA 101:13363-13367.
10. Johnson-Wood K, Lee M, Motter R, Hu K, Gordon G, Barbour R, Khan K, Gordon M, Tan H, Games D, Lieberburg I, Schenk D, Seubert P, McConlogue L (1997) Amyloid precursor protein processing and A beta42 deposition in a transgenic mouse model of Alzheimer disease. Proc Natl Acad Sci USA 94:1550-1555.
11. Koenigsknecht-Talboo J, Landreth GE (2005) Microglial phagocytosis induced by fibrillar β-amyloid and IgGs are differentially regulated by proinflammatory cytokines. J Neurosci 25:8240-8249.
12. Larsson E, Lindvall O, Kokaia Z (2001) Stereological assessment of vulnerability of immunocytochemically identified striatal and hippocampal neurons after global cerebral ischemia in rats. Brain Res 913:117-132.
13. Lemere CA, Spooner ET, Leverone JF, Mori C, Clements JD (2002) Intranasal immunotherapy for the treatment of Alzheimer's disease: Escherichia coli LT and LT(R192G) as mucosal adjuvants. Neurobiol Aging 23:991-1000.
14. Lemere CA, Spooner ET, LaFrancois J, Malester B, Mori C, Leverone JF, Matsuoka Y, Taylor JW, DeMattos RB, Holtzman DM, Clements JD, Selkoe DJ, Duff KE (2003) Evidence for peripheral clearance of Aβ following chronic, active Aβ immunization in PSAPP mice. Neurobiol Dis 14:10-18.
15. Lévi-Strauss M, Mallat M (1987) Primary cultures of murine astrocytes produce C3 and factor B, two components of the alternative pathway of complement activation. J Immunol 139:2361-2366.
16. Lledo PM, Alonso M, Grubb MS (2006) Adult neurogenesis and functional plasticity in neuronal circuits. Nat Rev Neurosci 7:179-193.
17. Maier M, Seabrook TJ, Lemere CA (2005) Modulation of the humoral and cellular immune response in Abeta immunotherapy by the adjuvants monophosphoryl lipid A (MPL), cholera toxin B subunit (CTB) and E. coli enterotoxin LT(R192G). Vaccine 23:5149-5159.
18. Maier M, Seabrook TJ, Lazo ND, Jiang L, Das P, Janus C, Lemere CA (2006) Short amyloid-β (Aβ) immunogens reduce cerebral Aβ load and learning deficits in an Alzheimer's disease mouse model in the absence of an Aβ-specific cellular immune response. J Neurosci 26:4717-4728.
19. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25:677-686.
20. Matsuoka Y, Picciano M, Malester B, LaFrancois J, Zehr C, Daeschner JM, Olschowka JA, Fonseca MI, O'Banion MK, Tenner AJ, Lemere CA, Duff K (2001) Inflammatory responses to amyloidosis in a transgenic mouse model of Alzheimer's disease. Am J Pathol 158:1345-1354.
21. McGeer PL, McGeer EG (2002) The possible role of complement activation in Alzheimer disease. Trends Mol Med 8:519-523.
22. McGeer PL, Akiyama H, Itagaki S, McGeer EG (1989) Activation of the classical complement pathway in brain tissue of Alzheimer patients. Neurosci Lett 107:341-346.
23. Morgan D, Gordon MN, Tan J, Wilcock D, Rojiani AM (2005) Dynamic complexity of microglial activation response in transgenic models of amyloid deposition: implications for Alzheimer's therapeutics. J Neuropathol Exp Neurol 64:743-753.
24. Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G, Hu K, Kholodenko D, Johnson-Wood K, McConlogue L (2000) High-level neuronal expression of Aβ1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci 20:4050-4058.
25. Mullen RJ, Buck CR, Smith AM (1992) NeuN, a neuronal specific nuclear protein in vertebrates. Development 116:201-211.
26. Osaka H, Mukherjee P, Aisen PS, Pasinetti GM (1999) Complement-derived anaphylatoxin C5a protects against glutamate-mediated neurotoxicity. J Cell Biochem 73:303-311.
27. Pasinetti GM, Tocco G, Sakhi S, Musleh WD, DeSimoni MG, Mascarucci P, Schreiber S, Baudry M, Finch CE (1996) 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.
28. Peng Y, Jiang L, Lee DY, Schachter SC, Ma Z, Lemere CA (2006) Effects of huperzine A on amyloid precursor protein processing and beta-amyloid generation in human embryonic kidney 293 APP Swedish mutant cells. J Neurosci Res 84:903-911.
29. Rahpeymai Y, Hietala MA, Wilhelmsson U, Fotheringham A, Davies I, Nilsson AK, Zwirner J, Wetsel RA, Gerard C, Pekny M, Pekna M (2006) Complement: a novel factor in basal and ischemia-induced neurogenesis. EMBO J 25:1364-1374.
30. Rogers J, Li R, Mastroeni D, Grover A, Leonard B, Ahern G, Cao P, Kolody H, Vedders L, Kolb WP, Sabbagh M (2006) Peripheral clearance of amyloid beta peptide by complement C3-dependent adherence to erythrocytes. Neurobiol Aging 27:1733-1739.
31. Shen Y, Li R, McGeer EG, McGeer PL (1997) Neuronal expression of mRNAs for complement proteins of the classical pathway in Alzheimer brain. Brain Res 769:391-395.
32. Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS, Nouri N, Micheva KD, Mehalow AK, Huberman AD, Stafford B, Sher A, Litke AM, Lambris JD, Smith SJ, John SW, Barres BA (2007) The classical complement cascade mediates CNS synapse elimination. Cell 131:1164-1178.
33. Stoltzner SE, Grenfell TJ, Mori C, Wisniewski KE, Wisniewski TM, Selkoe DJ, Lemere CA (2000) Temporal accrual of complement proteins in amyloid plaques in Down's syndrome with Alzheimer's disease. Am J Pathol 156:489-499.
34. Terai K, Walker DG, McGeer EG, McGeer PL (1997) Neurons express proteins of the classical complement pathway in Alzheimer disease. Brain Res 769:385-390.
35. Thomas A, Gasque P, Vaudry D, Gonzalez B, Fontaine M (2000) Expression of a complete and functional complement system by human neuronal cells in vitro. Int Immunol 12:1015-1023.
36. van Beek J, Elward K, Gasque P (2003) Activation of complement in the central nervous system: roles in neurodegeneration and neuroprotection. Ann NY Acad Sci 992:56-71.
37. Webster S, Bradt B, Rogers J, Cooper N (1997) Aggregation state-dependent activation of the classical complement pathway by the amyloid beta peptide. J Neurochem 69:388-398.
38. Wegiel J, Wisniewski HM (1990) The complex of microglial cells and amyloid star in three-dimensional reconstruction. Acta Neuropathol 81:116-124.
39. Wessels MR, Butko P, Ma M, Warren HB, Lage AL, Carroll MC (1995) Studies of group B streptococcal infection in mice deficient in complement component C3 or C4 demonstrate and essential role for complement in both innate and acquired immunity. Proc Natl Acad Sci USA 92:490-494.
40. West MJ, Gundersen HJ (1990) Unbiased stereological estimation of the number of neurons in the human hippocampus. J Comp Neurol 296:1-22.
41. Wilcock DM, Alamed J, Gottschall PE, Grimm J, Rosenthal A, Pons J, Ronan V, Symmonds K, Gordon MN, Morgan D (2006) Deglycosylated antiamyloid-β antibodies eliminate cognitive deficits and reduce parenchymal amyloid with minimal vascular consequences in aged amyloid precursor protein transgenic mice. J Neurosci 26:5340-5346.
42. Wyss-Coray T, Lin C, Yan F, Yu GQ, Rohde M, McConlogue L, Masliah E, Mucke L (2001) TGF-beta1 promotes microglial amyloid-beta clearance and reduces plaque burden in transgenic mice. Nat Med 7:612-618.
43. Wyss-Coray T, Yan F, Lin AH, Lambris JD, Alexander JJ, Quigg RJ, Masliah E (2002) Prominent neurodegeneration and increased plaque formation in complement-inhibited Alzheimer's mice. Proc Natl Acad Sci USA 99:10837-10842.
44. Yasojima K, Schwab C, McGeer EG, McGeer PL (1999) Up-regulated production and activation of the complement system in Alzheimer's disease brain. Am J Pathol 154:927-936.