Skip to main content
Erschienen in: Journal of Clinical Immunology 1/2014

01.07.2014

Intravenous Immunoglobulin (IVIG) Treatment Exerts Antioxidant and Neuropreservatory Effects in Preclinical Models of Alzheimer’s Disease

verfasst von: Scott E. Counts, Balmiki Ray, Elliott J. Mufson, Sylvia E. Perez, Bin He, Debomoy K. Lahiri

Erschienen in: Journal of Clinical Immunology | Sonderheft 1/2014

Einloggen, um Zugang zu erhalten

Abstract

Intravenous immunoglobulin (IVIG) has shown limited promise so far in human clinical studies on Alzheimer’s disease (AD), yet overwhelmingly positive preclinical work in animals and human brain cultures support the notion that the therapy remains potentially efficacious. Here, we elaborate on IVIG neuropreservation by demonstrating that IVIG protects human primary neurons against oxidative stress in vitro and that IVIG preserves antioxidant defense mechanisms in vivo. Based on these results, we propose the following translational impact: If the dosage and treatment conditions are adequately optimized, then IVIG treatment could play a significant role in preventing and/or delaying the progression of neurodegenerative diseases, such as AD. We suggest that IVIG warrants further investigation to fully exploit its potential as an anti-oxidant, neuroprotective and synapto-protecting agent.
Literatur
3.
Zurück zum Zitat Basha MR, Wei W, Bakheet SA, Benitez N, Siddiqi HK, Ge YW, et al. The fetal basis of amyloidogenesis: exposure to lead and latent overexpression of amyloid precursor protein and beta-amyloid in the aging brain. J Neurosci. 2005;25(4):823–9.PubMedCrossRef Basha MR, Wei W, Bakheet SA, Benitez N, Siddiqi HK, Ge YW, et al. The fetal basis of amyloidogenesis: exposure to lead and latent overexpression of amyloid precursor protein and beta-amyloid in the aging brain. J Neurosci. 2005;25(4):823–9.PubMedCrossRef
4.
Zurück zum Zitat Lahiri DK, Maloney B, Zawia NH. The LEARn model: an epigenetic explanation for idiopathic neurobiological diseases. Mol Psychiatry. 2009;14(11):992–1003. Nature Publishing Group.PubMedCrossRef Lahiri DK, Maloney B, Zawia NH. The LEARn model: an epigenetic explanation for idiopathic neurobiological diseases. Mol Psychiatry. 2009;14(11):992–1003. Nature Publishing Group.PubMedCrossRef
5.
6.
Zurück zum Zitat Perez FP, Bose D, Maloney B, Nho K, Shah K, Lahiri DK. Late-onset Alzheimer’s disease (LOAD) heating up and foxed by several proteins: pathomolecular efects of the aging process. J Alzheimer Dis. 2014;40(1):1–17. Perez FP, Bose D, Maloney B, Nho K, Shah K, Lahiri DK. Late-onset Alzheimer’s disease (LOAD) heating up and foxed by several proteins: pathomolecular efects of the aging process. J Alzheimer Dis. 2014;40(1):1–17.
7.
Zurück zum Zitat Alley GM, Bailey JA, Chen D, Ray B, Puli LK, Tanila H, et al. Memantine lowers amyloid-beta peptide levels in neuronal cultures and in APP/PS1 transgenic mice. J Neurosci Res. 2010;88(1):143–54.PubMedCentralPubMedCrossRef Alley GM, Bailey JA, Chen D, Ray B, Puli LK, Tanila H, et al. Memantine lowers amyloid-beta peptide levels in neuronal cultures and in APP/PS1 transgenic mice. J Neurosci Res. 2010;88(1):143–54.PubMedCentralPubMedCrossRef
8.
Zurück zum Zitat Bailey JA, Lahiri DK. A novel effect of rivastigmine on pre-synaptic proteins and neuronal viability in a neurodegeneration model of fetal rat primary cortical cultures and its implication in Alzheimer’s disease. J Neurochem. 2010;112(4):843–53.PubMedCentralPubMedCrossRef Bailey JA, Lahiri DK. A novel effect of rivastigmine on pre-synaptic proteins and neuronal viability in a neurodegeneration model of fetal rat primary cortical cultures and its implication in Alzheimer’s disease. J Neurochem. 2010;112(4):843–53.PubMedCentralPubMedCrossRef
9.
Zurück zum Zitat Bailey JA, Ray B, Greig NH, Lahiri DK. Rivastigmine lowers Aβ and increases sAPPalpha levels, which parallel elevated synaptic markers and metabolic activity in degenerating primary rat neurons. PLoS ONE. 2011;6(7):e21954.PubMedCentralPubMedCrossRef Bailey JA, Ray B, Greig NH, Lahiri DK. Rivastigmine lowers Aβ and increases sAPPalpha levels, which parallel elevated synaptic markers and metabolic activity in degenerating primary rat neurons. PLoS ONE. 2011;6(7):e21954.PubMedCentralPubMedCrossRef
10.
Zurück zum Zitat Ray B, Chauhan NB, Lahiri DK. Oxidative insults to neurons and synapse are prevented by AGE and SAC treatment in the neuronal culture and APP-Tg mouse model. J Neurochem. 2011;117(3):388–402.PubMedCentralPubMedCrossRef Ray B, Chauhan NB, Lahiri DK. Oxidative insults to neurons and synapse are prevented by AGE and SAC treatment in the neuronal culture and APP-Tg mouse model. J Neurochem. 2011;117(3):388–402.PubMedCentralPubMedCrossRef
11.
Zurück zum Zitat Farlow MR, Brosch JR. Immunotherapy for Alzheimer’s disease. Neurol Clin. 2013;31(3):869–78.PubMedCrossRef Farlow MR, Brosch JR. Immunotherapy for Alzheimer’s disease. Neurol Clin. 2013;31(3):869–78.PubMedCrossRef
12.
Zurück zum Zitat Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, et al. Long-term effects ofAbeta42 immunisation in Alzheimer’s disease: follow-up of a randomised, placebo-controlledphase I trial. Lancet. 2008;372:216–23.PubMedCrossRef Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, et al. Long-term effects ofAbeta42 immunisation in Alzheimer’s disease: follow-up of a randomised, placebo-controlledphase I trial. Lancet. 2008;372:216–23.PubMedCrossRef
13.
Zurück zum Zitat Salloway S, Sperling R, Gilman S, Fox NC, Blennow K, Raskind M, et al. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology. 2009;73:2061–70.PubMedCentralPubMedCrossRef Salloway S, Sperling R, Gilman S, Fox NC, Blennow K, Raskind M, et al. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology. 2009;73:2061–70.PubMedCentralPubMedCrossRef
14.
Zurück zum Zitat Gilman S, Koller M, Black RS, Jenkins L, Griffith SG, Fox NC, et al. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology. 2005;64:1553–62.PubMedCrossRef Gilman S, Koller M, Black RS, Jenkins L, Griffith SG, Fox NC, et al. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology. 2005;64:1553–62.PubMedCrossRef
15.
Zurück zum Zitat Dodel R, Neff F, Noelker C, Pul R, Du Y, Bacher M, et al. Intravenous immunoglobulins as atreatment for Alzheimer’s disease: rationale and current evidence. Drugs. 2010;70:513–28.PubMedCrossRef Dodel R, Neff F, Noelker C, Pul R, Du Y, Bacher M, et al. Intravenous immunoglobulins as atreatment for Alzheimer’s disease: rationale and current evidence. Drugs. 2010;70:513–28.PubMedCrossRef
16.
Zurück zum Zitat Relkin NR, Szabo P, Adamiak B, Burgut T, Monthe C, Lent RW, et al. 18-Month study ofintravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol Aging. 2009;30:1728–36.PubMedCrossRef Relkin NR, Szabo P, Adamiak B, Burgut T, Monthe C, Lent RW, et al. 18-Month study ofintravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol Aging. 2009;30:1728–36.PubMedCrossRef
18.
Zurück zum Zitat Magga J, Puli L, Pihlaja R, et al. Human intravenous immunoglobulin provides protection against Abeta toxicity by multiple mechanisms in a mouse model of Alzheimer’s disease. J Neuroinflammation. 2010;7:90.PubMedCentralPubMedCrossRef Magga J, Puli L, Pihlaja R, et al. Human intravenous immunoglobulin provides protection against Abeta toxicity by multiple mechanisms in a mouse model of Alzheimer’s disease. J Neuroinflammation. 2010;7:90.PubMedCentralPubMedCrossRef
19.
Zurück zum Zitat Puli L, Pomeshchik Y, Olas K, Malm T, Koistinaho J, Tanila H. Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease. J Neuroinflammation. 2012;9:105.PubMedCentralPubMedCrossRef Puli L, Pomeshchik Y, Olas K, Malm T, Koistinaho J, Tanila H. Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease. J Neuroinflammation. 2012;9:105.PubMedCentralPubMedCrossRef
20.
Zurück zum Zitat Counts S, Perez S, He B, Mufson E. Intravenous immunoglobulin reduces tau pathology and preserves neuroplastic gene expression in the 3xTg mouse model of Alzheimer’s disease. Current Alz Res. 2014; In press. Counts S, Perez S, He B, Mufson E. Intravenous immunoglobulin reduces tau pathology and preserves neuroplastic gene expression in the 3xTg mouse model of Alzheimer’s disease. Current Alz Res. 2014; In press.
21.
Zurück zum Zitat Sudduth TL, Greenstein A, Wilcock DM. Intracranial injection of Gammagard, a human IVIg, modulates the inflammatory response of the brain and lowers Aβ in APP/PS1 mice along a different time course than anti-Aβ antibodies. J Neurosci. 2013;33(23):9684–92.PubMedCentralPubMedCrossRef Sudduth TL, Greenstein A, Wilcock DM. Intracranial injection of Gammagard, a human IVIg, modulates the inflammatory response of the brain and lowers Aβ in APP/PS1 mice along a different time course than anti-Aβ antibodies. J Neurosci. 2013;33(23):9684–92.PubMedCentralPubMedCrossRef
22.
Zurück zum Zitat Bailey JA, Ray B, Lahiri DK. Intravenous immunoglobulin (IVIG) protects neuronal viability and synaptic markers in cultured degenerating primary hippocampal neurons. Societ Neurosci Abst. 2012;852.04. Bailey JA, Ray B, Lahiri DK. Intravenous immunoglobulin (IVIG) protects neuronal viability and synaptic markers in cultured degenerating primary hippocampal neurons. Societ Neurosci Abst. 2012;852.04.
23.
Zurück zum Zitat Lahiri DK, Ray B. Effect of IVIG in preserving human primary neurons and protecting them against oxidative stress. Alzheimers Dement. 2013;9(4):800.CrossRef Lahiri DK, Ray B. Effect of IVIG in preserving human primary neurons and protecting them against oxidative stress. Alzheimers Dement. 2013;9(4):800.CrossRef
24.
Zurück zum Zitat Lahiri DK, Ray B. Intravenous Immunoglobulin (IVIG) treatment exerts a protective effect against oxidative insults in primary human neuronal mixed cultures. Curr Alzheimer Res. 2014; In press. Lahiri DK, Ray B. Intravenous Immunoglobulin (IVIG) treatment exerts a protective effect against oxidative insults in primary human neuronal mixed cultures. Curr Alzheimer Res. 2014; In press.
25.
Zurück zum Zitat Long JM, Ray B, Lahiri DK. MicroRNA-153 physiologically inhibits expression of amyloid-beta precursor protein in cultured human fetal brain cells and is dysregulated in a subset of Alzheimer disease patients. J Biol Chem. 2012;28(37):31298–310.CrossRef Long JM, Ray B, Lahiri DK. MicroRNA-153 physiologically inhibits expression of amyloid-beta precursor protein in cultured human fetal brain cells and is dysregulated in a subset of Alzheimer disease patients. J Biol Chem. 2012;28(37):31298–310.CrossRef
26.
Zurück zum Zitat Counts SE, Che S, Ginsberg SD, Mufson EJ. Gender differences in neurotrophin and glutamate receptor expression in cholinergic nucleus basalis neurons during the progression of Alzheimer’s disease. J Chem Neuroanat. 2011;42:111–7.PubMedCentralPubMedCrossRef Counts SE, Che S, Ginsberg SD, Mufson EJ. Gender differences in neurotrophin and glutamate receptor expression in cholinergic nucleus basalis neurons during the progression of Alzheimer’s disease. J Chem Neuroanat. 2011;42:111–7.PubMedCentralPubMedCrossRef
27.
Zurück zum Zitat Ginsberg SD, Alldred MJ, Counts SE, Cataldo AM, Neve RL, Jiang Y, et al. Microarray analysis of hippocampal CA1 neurons implicates early endosomal dysfunction during Alzheimer’s disease progression. Biol Psychiatry. 2010;68:885–93.PubMedCentralPubMedCrossRef Ginsberg SD, Alldred MJ, Counts SE, Cataldo AM, Neve RL, Jiang Y, et al. Microarray analysis of hippocampal CA1 neurons implicates early endosomal dysfunction during Alzheimer’s disease progression. Biol Psychiatry. 2010;68:885–93.PubMedCentralPubMedCrossRef
Metadaten
Titel
Intravenous Immunoglobulin (IVIG) Treatment Exerts Antioxidant and Neuropreservatory Effects in Preclinical Models of Alzheimer’s Disease
verfasst von
Scott E. Counts
Balmiki Ray
Elliott J. Mufson
Sylvia E. Perez
Bin He
Debomoy K. Lahiri
Publikationsdatum
01.07.2014
Verlag
Springer US
Erschienen in
Journal of Clinical Immunology / Ausgabe Sonderheft 1/2014
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-014-0020-9

Weitere Artikel der Sonderheft 1/2014

Journal of Clinical Immunology 1/2014 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.