Top

Journal of Neuroinflammation

Published in:

Open Access 01-12-2012 | Research

Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease

Authors: Lakshman Puli, Yuriy Pomeshchik, Katja Olas, Tarja Malm, Jari Koistinaho, Heikki Tanila

Published in: Journal of Neuroinflammation | Issue 1/2012

Abstract

Background

Human intravenous immunoglobulin (hIVIG) preparation is indicated for treating primary immunodeficiency disorders associated with impaired humoral immunity. hIVIG is known for its anti-inflammatory properties and a decent safety profile. Therefore, by virtue of its constituent natural anti-amyloid beta antibodies and anti-inflammatory effects, hIVIG is deemed to mediate beneficial effects to patients of Alzheimer’s disease (AD). Here, we set out to explore the effects of hIVIG in a mouse model of AD.

Methods

We treated APP/PS1dE9 transgenic and wild-type mice with weekly injections of a high hIVIG dose (1 g/kg) or saline for 3 or 8 months. Treatment effect on brain amyloid pathology and microglial reactivity was assessed by ELISA, immunohistochemistry, RT-PCR, and confocal microscopy.

Results

We found no evidence for reduction in Aβ pathology; instead 8 months of hIVIG treatment significantly increased soluble levels of Aβ40 and Aβ42. In addition, we noticed a significant reduction in CD45 and elevation of Iba-1 markers in specific sub-populations of microglial cells. Long-term hIVIG treatment also resulted in significant suppression of TNF-α and increase in doublecortin positive adult-born neurons in the dentate gyrus.

Conclusions

Our data indicate limited ability of hIVIG to impact amyloid burden but shows changes in microglia, pro-inflammatory gene expression, and neurogenic effects. Immunomodulation by hIVIG may account for its beneficial effect in AD patients.

Hardy JA, Higgins GA: Alzheimer’s disease: the amyloid cascade hypothesis. Science 1992, 256:184–185.CrossRefPubMed

Morgan D: The role of microglia in antibody-mediated clearance of amyloid-beta from the brain. CNS Neurol Disord Drug Targets 2009, 8:7–15.CrossRefPubMed

Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE, Frautschy S, Griffin WS, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie IR, McGeer PL, O’Banion MK, Pachter J, Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Streit W, Strohmeyer R, Tooyoma I, et al.: Inflammation and Alzheimer’s disease. Neurobiol Aging 2000, 21:383–421.CrossRefPubMedPubMedCentral

Wang Q, Wu J, Rowan MJ, Anwyl R: Beta-amyloid inhibition of long-term potentiation is mediated via tumor necrosis factor. Eur J Neurosci 2005, 22:2827–2832.CrossRefPubMed

Lyons A, Griffin RJ, Costelloe CE, Clarke RM, Lynch MA: IL-4 attenuates the neuroinflammation induced by amyloid-beta in vivo and in vitro. J Neurochem 2007, 101:771–781.CrossRefPubMed

Hickman SE, Allison EK: El Khoury J: Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer’s disease mice. J Neurosci 2008, 28:8354–8360.CrossRefPubMedPubMedCentral

Malm TM, Koistinaho M, Parepalo M, Vatanen T, Ooka A, Karlsson S, Koistinaho J: Bone-marrow-derived cells contribute to the recruitment of microglial cells in response to beta-amyloid deposition in APP/PS1 double transgenic Alzheimer mice. Neurobiol Dis 2005, 18:134–142.CrossRefPubMed

Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, Guido T, Hu K, Huang J, Johnson-Wood K, Khan K, Kholodenko D, Lee M, Liao Z, Lieberburg I, Motter R, Mutter L, Soriano F, Shopp G, Vasquez N, Vandevert C, Walker S, Wogulis M, Yednock T, Games D, Seubert P: Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 1999, 400:173–177.CrossRefPubMed

Morgan D, Diamond DM, Gottschall PE, Ugen KE, Dickey C, Hardy J, Duff K, Jantzen P, DiCarlo G, Wilcock D, Connor K, Hatcher J, Hope C, Gordon M, Arendash GW: A beta peptide vaccination prevents memory loss in an animal model of Alzheimer’s disease. Nature 2000, 408:982–985.CrossRefPubMed

10.

Janus C, Pearson J, McLaurin J, Mathews PM, Jiang Y, Schmidt SD, Chishti MA, Horne P, Heslin D, French J, Mount HT, Nixon RA, Mercken M, Bergeron C, Fraser PE, St George-Hyslop P, Westaway D: A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer’s disease. Nature 2000, 408:979–982.CrossRefPubMed

11.

Orgogozo JM, Gilman S, Dartigues JF, Laurent B, Puel M, Kirby LC, Jouanny P, Dubois B, Eisner L, Flitman S, Michel BF, Boada M, Frank A, Hock C: Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology 2003, 61:46–54.CrossRefPubMed

12.

Wilcock DM, Rojiani A, Rosenthal A, Levkowitz G, Subbarao S, Alamed J, Wilson D, Wilson N, Freeman MJ, Gordon MN, Morgan D: Passive amyloid immunotherapy clears amyloid and transiently activates microglia in a transgenic mouse model of amyloid deposition. J Neurosci 2004, 24:6144–6151.CrossRefPubMed

13.

Levites Y, Das P, Price RW, Rochette MJ, Kostura LA, McGowan EM, Murphy MP, Golde TE: Anti-Abeta42- and anti-Abeta40-specific mAbs attenuate amyloid deposition in an Alzheimer disease mouse model. J Clin Invest 2006, 116:193–201.CrossRefPubMed

14.

Bard F, Cannon C, Barbour R, Burke RL, Games D, Grajeda H, Guido T, Hu K, Huang J, Johnson-Wood K, Khan K, Kholodenko D, Lee M, Lieberburg I, Motter R, Nguyen M, Soriano F, Vasquez N, Weiss K, Welch B, Seubert P, Schenk D, Yednock T: Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat Med 2000, 6:916–919.CrossRefPubMed

15.

Pfeifer M, Boncristiano S, Bondolfi L, Stalder A, Deller T, Staufenbiel M, Mathews PM, Jucker M: Cerebral hemorrhage after passive anti-Abeta immunotherapy. Science 2002, 298:1379.CrossRefPubMed

16.

Salloway S, Sperling R, Gilman S, Fox NC, Blennow K, Raskind M, Sabbagh M, Honig LS, Doody R, van Dyck CH, Mulnard R, Barakos J, Gregg KM, Liu E, Lieberburg I, Schenk D, Black R, Grundman M: Bapineuzumab 201 Clinical Trial Investigators :A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology 2009, 73:2061–2070.CrossRefPubMedPubMedCentral

17.

van Doorn PA, Kuitwaard K, Walgaard C, van Koningsveld R, Ruts L, Jacobs BC: IVIG treatment and prognosis in Guillain-Barre syndrome. J Clin Immunol 2010, 1:S74-S78.CrossRef

18.

O’Nuallain B, Acero L, Williams AD, Koeppen HP, Weber A, Schwarz HP, Wall JS, Weiss DT, Solomon A: Human plasma contains cross-reactive Abeta conformer-specific IgG antibodies. Biochemistry 2008, 47:12254–12256.CrossRefPubMed

19.

Dodel RC, Du Y, Depboylu C, Hampel H, Frolich L, Haag A, Hemmeter U, Paulsen S, Teipel SJ, Brettschneider S, Spottke A, Nolker C, Moller HJ, Wei X, Farlow M, Sommer N, Oertel WH: Intravenous immunoglobulins containing antibodies against beta-amyloid for the treatment of Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2004, 75:1472–1474.CrossRefPubMedPubMedCentral

20.

Relkin NR, Szabo P, Adamiak B, Burgut T, Monthe C, Lent RW, Younkin S, Younkin L, Schiff R, Weksler ME: 18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol Aging 2009, 30:1728–1736.CrossRefPubMed

21.

Magga J, Puli L, Pihlaja R, Kanninen K, Neulamaa S, Malm T, Hartig W, Grosche J, Goldsteins G, Tanila H, Koistinaho J, Koistinaho M: Human intravenous immunoglobulin provides protection against Abeta toxicity by multiple mechanisms in a mouse model of Alzheimer’s disease. J Neuroinflammation 2010, 7:90.CrossRefPubMedPubMedCentral

22.

Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA, Copeland NG, Lee MK, Younkin LH, Wagner SL, Younkin SG, Borchelt DR: Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet 2004, 13:159–170.CrossRefPubMed

23.

Garcia-Alloza M, Robbins EM, Zhang-Nunes SX, Purcell SM, Betensky RA, Raju S, Prada C, Greenberg SM, Bacskai BJ, Frosch MP: Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease. Neurobiol Dis 2006, 24:516–524.CrossRefPubMed

24.

Dodel R, Balakrishnan K, Keyvani K, Deuster O, Neff F, Andrei-Selmer LC, Roskam S, Stuer C, Al-Abed Y, Noelker C, Balzer-Geldsetzer M, Oertel W, Du Y, Bacher M: Naturally occurring autoantibodies against beta-amyloid: investigating their role in transgenic animal and in vitro models of Alzheimer’s disease. J Neurosci 2011, 31:5847–5854.CrossRefPubMed

25.

Kettenmann H, Hanisch UK, Noda M, Verkhratsky A: Physiology of microglia. Physiol Rev 2011, 91:461–553.CrossRefPubMed

26.

Guillemin GJ, Brew BJ: Microglia, macrophages, perivascular macrophages, and pericytes: a review of function and identification. J Leukoc Biol 2004, 75:388–397.CrossRefPubMed

27.

Duffield JS: The inflammatory macrophage: a story of Jekyll and Hyde. Clin Sci (Lond) 2003, 104:27–38.CrossRef

28.

Naert G, Rivest S: The role of microglial cell subsets in Alzheimer’s disease. Curr Alzheimer Res 2011, 8:151–155.CrossRefPubMed

29.

Hanisch UK, Kettenmann H: Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 2007, 10:1387–94.CrossRefPubMed

30.

Biscaro B, Lindvall O, Hock C, Ekdahl CT, Nitsch RM: Abeta immunotherapy protects morphology and survival of adult-born neurons in doubly transgenic APP/PS1 mice. J Neurosci 2009, 29:14108–14119.CrossRefPubMed

31.

Das S, Basu A: Inflammation: a new candidate in modulating adult neurogenesis. J Neurosci Res 2008, 86:1199–1208.CrossRefPubMed

32.

Ekdahl CT, Claasen JH, Bonde S, Kokaia Z, Lindvall O: Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci U S A 2003, 100:13632–13637.CrossRefPubMedPubMedCentral

33.

Ekdahl CT, Kokaia Z, Lindvall O: Brain inflammation and adult neurogenesis: the dual role of microglia. Neuroscience 2009, 158:1021–1029.CrossRefPubMed

34.

Monje ML, Toda H, Palmer TD: Inflammatory blockade restores adult hippocampal neurogenesis. Science 2003, 302:1760–1765.CrossRefPubMed

35.

Battista D, Ferrari CC, Gage FH, Pitossi FJ: Neurogenic niche modulation by activated microglia: transforming growth factor beta increases neurogenesis in the adult dentate gyrus. Eur J Neurosci 2006, 23:83–93.CrossRefPubMed

36.

Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M: Alzheimer’s disease: clinical trials and drug development. Lancet Neurol 2010, 9:702–716.CrossRefPubMed

37.

O’Nuallain B, Williams AD, McWilliams-Koeppen HP, Acero L, Weber A, Ehrlich H, Schwarz HP, Solomon A: Anti-amyloidogenic activity of IgGs contained in normal plasma. J Clin Immunol 2010, 1:S37-S42.CrossRef

38.

Solomon B: Beta-amyloidbased immunotherapy as a treatment of Alzheimer’s disease. Drugs Today (Barc) 2007, 43:333–342.CrossRef

39.

Grathwohl SA, Kalin RE, Bolmont T, Prokop S, Winkelmann G, Kaeser SA, Odenthal J, Radde R, Eldh T, Gandy S, Aguzzi A, Staufenbiel M, Mathews PM, Wolburg H, Heppner FL, Jucker M: Formation and maintenance of Alzheimer’s disease beta-amyloid plaques in the absence of microglia. Nat Neurosci 2009, 12:1361–1363.CrossRefPubMedPubMedCentral

40.

Zhu Y, Hou H, Rezai-Zadeh K, Giunta B, Ruscin A, Gemma C, Jin J, Dragicevic N, Bradshaw P, Rasool S, Glabe CG, Ehrhart J, Bickford P, Mori T, Obregon D, Town T, Tan J: CD45 deficiency drives amyloid-beta peptide oligomers and neuronal loss in Alzheimer’s disease mice. J Neurosci 2011, 31:1355–1365.CrossRefPubMedPubMedCentral

41.

DeMattos RB, Bales KR, Cummins DJ, Dodart JC, Paul SM, Holtzman DM: Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci U S A 2001, 98:8850–8855.CrossRefPubMedPubMedCentral

42.

Winkler DT, Abramowski D, Danner S, Zurini M, Paganetti P, Tolnay M, Staufenbiel M: Rapid cerebral amyloid binding by Abeta antibodies infused into beta-amyloid precursor protein transgenic mice. Biol Psychiatry 2010, 68:971–974.CrossRefPubMed

43.

Levites Y, Smithson LA, Price RW, Dakin RS, Yuan B, Sierks MR, Kim J, McGowan E, Reed DK, Rosenberry TL, Das P, Golde TE: Insights into the mechanisms of action of anti-Abeta antibodies in Alzheimer's disease mouse models. FASEB J 2006, 20:2576–2578.CrossRefPubMed

44.

Blennow K, Zetterberg H, Rinne JO, Salloway S, Wei J, Black R, Grundman M, Liu E, for the AAB-001 201/202 Investigators, for the AAB-001 201/202 Investigators: Effect of Immunotherapy With Bapineuzumab on Cerebrospinal Fluid Biomarker Levels in Patients With Mild to Moderate Alzheimer Disease. Arch Neurol 2012.

45.

Kondo M, Tokuda T, Kasai T, Oishi Y, Ataka S, Shimada H, Miki T, Mori H, Nakagawa M: Intravenous immunoglobulin improved cognitive functions in patients with Alzheimer’s disease without any changes in PIB retention in the brain. Alzheimers Dement 2011, 7:S791.CrossRef

46.

Nimmerjahn F, Ravetch JV: Anti-inflammatory actions of intravenous immunoglobulin. Annu Rev Immunol 2008, 26:513–33.CrossRefPubMed

47.

Masliah E, Mallory M, Hansen L, Alford M, Albright T, Terry R, Shapiro P, Sundsmo M, Saitoh T: Immunoreactivity of CD45, a protein phosphotyrosine phosphatase, in Alzheimer’s disease. Acta Neuropathol 1991, 83:12–20.CrossRefPubMed

48.

Istrin G, Bosis E, Solomon B: Intravenous immunoglobulin enhances the clearance of fibrillar amyloid-beta peptide. J Neurosci Res 2006, 84:434–43.CrossRefPubMed

49.

Murakami K, Suzuki C, Fujii A, Imada T: Intravenous immunoglobulin prevents release of pro-inflammatory cytokines in human monocytic cells stimulated with procalcitonin. Inflamm Res 2012, 61:617–622.CrossRefPubMed

50.

Toungouz M, Denys CH, De Groote D, Dupont E: In vitro inhibition of tumour necrosis factor-alpha and interleukin-6 production by intravenous immunoglobulins. Br J Haematol 1995, 89:698–703.CrossRefPubMed

51.

Andersson JP, Andersson UG: Human intravenous immunoglobulin modulates monokine production in vitro. Immunology 1990, 71:372–376.PubMedPubMedCentral

52.

Yang HT, Wang Y, Zhao X, Demissie E, Papoutsopoulou S, Mambole A, O’Garra A, Tomczak MF, Erdman SE, Fox JG, Ley SC, Horwitz BH: NF-{kappa}B1 Inhibits TLR-Induced IFN-{beta} Production in Macrophages through TPL-2-Dependent ERK Activation. J Immunol 2011, 186:1989–1996.CrossRefPubMedPubMedCentral

53.

Wu KH, Wu WM, Lu MY, Chiang BL: Inhibitory effect of pooled human immunoglobulin on cytokine production in peripheral blood mononuclear cells. Pediatr Allergy Immunol 2006, 17:60–68.CrossRefPubMed

54.

Toyoda M, Zhang X, Petrosian A, Galera OA, Wang SJ, Jordan SC: Modulation of immunoglobulin production and cytokine mRNA expression in peripheral blood mononuclear cells by intravenous immunoglobulin. J Clin Immunol 1994, 14:178–89.CrossRefPubMed

55.

Aukrust P, Froland SS, Liabakk NB, Muller F, Nordoy I, Haug C, Espevik T: Release of cytokines, soluble cytokine receptors, and interleukin-1 receptor antagonist after intravenous immunoglobulin administration in vivo. Blood 1994, 84:2136–43.PubMed

56.

Ling ZD, Yeoh E, Webb BT, Farrell K, Doucette J, Matheson DS: Intravenous immunoglobulin induces interferon-gamma and interleukin-6 in vivo. J Clin Immunol 1993, 13:302–309.CrossRefPubMed

57.

Wadhwa M, Meager A, Dilger P, Bird C, Dolman C, Das RG, Thorpe R: Neutralizing antibodies to granulocyte-macrophage colony-stimulating factor, interleukin-1alpha and interferon-alpha but not other cytokines in human immunoglobulin preparations. Immunology 2000, 99:113–23.CrossRefPubMedPubMedCentral

58.

Andersson J, Skansen-Saphir U, Sparrelid E, Andersson U: Intravenous immune globulin affects cytokine production in T lymphocytes and monocytes/macrophages. Clin Exp Immunol 1996, 1:10–20.

59.

Le Pottier L, Sapir T, Bendaoud B, Youinou P, Shoenfeld Y, Pers JO: Intravenous immunoglobulin and cytokines: focus on tumor necrosis factor family members BAFF and APRIL. Ann N Y Acad Sci 2007, 1110:426–32.CrossRefPubMed

60.

Ruan L, Kang Z, Pei G, Le Y: Amyloid deposition and inflammation in APPswe/PS1dE9 mouse model of Alzheimer’s disease. Curr Alzheimer Res 2009, 6:531–540.CrossRefPubMed

61.

Sharief MK, Ingram DA, Swash M, Thompson EJ: I.v. immunoglobulin reduces circulating pro-inflammatory cytokines in Guillain-Barre syndrome. Neurology 1999, 52:1833–1838.CrossRefPubMed

62.

Song C, Wang H: Cytokines mediated inflammation and decreased neurogenesis in animal models of depression. Prog Neuropsychopharmacol Biol Psychiatry 2011, 35:760–768.CrossRefPubMed

63.

Cameron HA, Gould E: Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus. Neuroscience 1994, 61:203–209.CrossRefPubMed

64.

Mehler MF, Rozental R, Dougherty M, Spray DC, Kessler JA: Cytokine regulation of neuronal differentiation of hippocampal progenitor cells. Nature 1993, 362:62–65.CrossRefPubMed

65.

van der Borght K, Kohnke R, Goransson N, Deierborg T, Brundin P, Erlanson-Albertsson C, Lindqvist A: Reduced neurogenesis in the rat hippocampus following high fructose consumption. Regul Pept 2011, 167:26–30.CrossRefPubMed

66.

Iosif RE, Ekdahl CT, Ahlenius H, Pronk CJ, Bonde S, Kokaia Z, Jacobsen SE, Lindvall O: Tumor necrosis factor receptor 1 is a negative regulator of progenitor proliferation in adult hippocampal neurogenesis. J Neurosci 2006, 26:9703–9712.CrossRefPubMed

67.

Goshen I, Kreisel T, Ben-Menachem-Zidon O, Licht T, Weidenfeld J, Ben-Hur T, Yirmiya R: Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression. Mol Psychiatry 2008, 13:717–728.CrossRefPubMed

68.

Koo JW, Duman RS: IL-1beta is an essential mediator of the antineurogenic and anhedonic effects of stress. Proc Natl Acad Sci U S A 2008, 105:751–756.CrossRefPubMedPubMedCentral

69.

Kaneko N, Kudo K, Mabuchi T, Takemoto K, Fujimaki K, Wati H, Iguchi H, Tezuka H, Kanba S: Suppression of cell proliferation by interferon-alpha through interleukin-1 production in adult rat dentate gyrus. Neuropsychopharmacology 2006, 31:2619–2626.CrossRefPubMed

70.

Vallieres L, Campbell IL, Gage FH, Sawchenko PE: Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6. J Neurosci 2002, 22:486–492.PubMed

71.

Zunszain PA, Anacker C, Cattaneo A, Choudhury S, Musaelyan K, Myint AM, Thuret S, Price J, Pariante CM: Interleukin-1beta: a new regulator of the kynurenine pathway affecting human hippocampal neurogenesis. Neuropsychopharmacology 2012, 37:939–949.CrossRefPubMed

72.

Seguin JA, Brennan J, Mangano E, Hayley S: Pro-inflammatory cytokines differentially influence adult hippocampal cell proliferation depending upon the route and chronicity of administration. Neuropsychiatr Dis Treat 2009, 5:5–14.PubMedPubMedCentral

73.

Galvan V, Bredesen DE: Neurogenesis in the adult brain: implications for Alzheimer’s disease. CNS Neurol Disord Drug Targets 2007, 6:303–310.CrossRefPubMed

74.

Monje ML, Mizumatsu S, Fike JR, Palmer TD: Irradiation induces neural precursor-cell dysfunction. Nat Med 2002, 8:955–962.CrossRefPubMed

75.

Liu Z, Fan Y, Won SJ, Neumann M, Hu D, Zhou L, Weinstein PR, Liu J: Chronic treatment with minocycline preserves adult new neurons and reduces functional impairment after focal cerebral ischemia. Stroke 2007, 38:146–152.CrossRefPubMed

76.

Butovsky O, Ziv Y, Schwartz A, Landa G, Talpalar AE, Pluchino S, Martino G, Schwartz M: Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells. Mol Cell Neurosci 2006, 31:149–160.CrossRefPubMed

77.

Ziv Y, Ron N, Butovsky O, Landa G, Sudai E, Greenberg N, Cohen H, Kipnis J, Schwartz M: Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat Neurosci 2006, 9:268–275.CrossRefPubMed

78.

Carro E, Trejo JL, Busiguina S, Torres-Aleman I: Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy. J Neurosci 2001, 21:5678–5684.PubMed

79.

Trejo JL, Carro E, Torres-Aleman I: Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J Neurosci 2001, 21:1628–1634.PubMed

80.

Schnabel J: Vaccines: chasing the dream. Nature. 2011, 475:S18-S19.PubMed

81.

Relkin N, Backes L, Schiff R: Changes in plasma cytokine levels correlate with clinical outcomes in Alzheimer’s patients treated with intravenous immunoglobulin. Alzheimers Dement 2011, 7:S693.CrossRef

82.

Selkoe DJ: Resolving controversies on the path to Alzheimer’s therapeutics. Nat Med 2011, 17:1060–1065.CrossRefPubMed

83.

Ballow M: The IgG molecule as a biological immune response modifier: mechanisms of action of intravenous immune serum globulin in autoimmune and inflammatory disorders. J Allergy Clin Immunol 2011,127(315):23. quiz 324–325

84.

Bayry J, Kazatchkine MD, Kaveri SV: Shortage of human intravenous immunoglobulin–reasons and possible solutions. Nat Clin Pract Neurol 2007, 3:120–121.CrossRefPubMed

85.

Anthony RM, Kobayashi T, Wermeling F, Ravetch JV: Intravenous gammaglobulin suppresses inflammation through a novel T(H)2 pathway. Nature 2011, 475:110–113.CrossRefPubMedPubMedCentral

Title: Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease
Authors: Lakshman Puli
Yuriy Pomeshchik
Katja Olas
Tarja Malm
Jari Koistinaho
Heikki Tanila
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2012
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/1742-2094-9-105

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2012

IFN-γ-induced increase in the mobility of MHC class II compartments in astrocytes depends on intermediate filaments

Chemokine CCL2 and its receptor CCR2 in the medullary dorsal horn are involved in trigeminal neuropathic pain

Blockade of interleukin-6 signaling inhibits the classic pathway and promotes an alternative pathway of macrophage activation after spinal cord injury in mice

5, 8, 11, 14-eicosatetraynoic acid suppresses CCL2/MCP-1 expression in IFN-γ-stimulated astrocytes by increasing MAPK phosphatase-1 mRNA stability

Deficiency of terminal complement pathway inhibitor promotes neuronal tau pathology and degeneration in mice

Delayed mGluR5 activation limits neuroinflammation and neurodegeneration after traumatic brain injury