Hippocampal expression of murine IL-4 results in exacerbation of amyloid deposition
Open accessAbstract
Background: Pro-inflammatory stimuli, including cytokines like Interleukin-1β, Interleukin-6 and Interferon-γ, in the brain have been proposed to exacerbate existing Alzheimer’s disease (AD) neuropathology by increasing amyloidogenic processing of APP and promoting further Aβ accumulation in AD. On the other hand, anti-inflammatory cytokines have been suggested to be neuroprotective by reducing neuroinflammation and clearing Aβ. To test this hypothesis, we used adeno-associated virus serotype 1 (AAV2/1) to express an anti-inflammatory cytokine, murine Interleukin-4 (mIL-4), in the hippocampus of APP transgenic TgCRND8 mice with pre-existing plaques. Results: mIL-4 expression resulted in establishment of an “M2-like” phenotype in the brain and was accompanied by exacerbated Aβ deposition in TgCRND8 mice brains. No change in holo APP or APP C terminal fragment or phosphorylated tau levels were detected in mIL-4 expressing CRND8 cohorts. Biochemical analysis shows increases in both SDS soluble and insoluble Aβ. mIL-4 treatment attenuates soluble Aβ40 uptake by microglia but does not affect aggregated Aβ42 internalization by microglia or soluble Aβ40 internalization by astrocytes. Conclusions: Short term focal mIL-4 expression in the hippocampus leads to exacerbation of amyloid deposition in vivo, possibly mediated by acute suppression of glial clearance mechanisms. Given that recent preclinical data from independent groups indicate engagement of the innate immune system early on during disease pathogenesis may be beneficial, our present study strongly argues for a cautious re-examination of unwarranted side–effects of anti-inflammatory therapies for neurodegenerative diseases, including AD.
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Microglial cells play pivotal role in maintaining immunoproteostasis through phagocytosis and degradation of misfolded proteins, their protective function is inseparably associated with immune activation exerting a chronic, potentially harmful effect on the regional milieu of neuronal networks.
“Though microglial cells play pivotal role in maintaining immunoproteostasis through phagocytosis and degradation of misfolded proteins, their protective function is inseparably associated with immune activation exerting a chronic, potentially harmful effect on the regional milieu of neuronal networks [35, 37–39].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [37]
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Cites
Bard, F., Cannon, C., Barbour, R., Burke, R.-L., Games, D., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., et al. (2000) · Nature Medicine · doi:10.1038/78682 · Cited by 2,012 · see citing works
Stewart, C. R., Stuart, L. M., Wilkinson, K., van Gils, J. M., Deng, J., Halle, A., Rayner, K. J., Boyer, L., Zhong, R., Frazier, W. A., et al. (2010) · Nature Immunology · doi:10.1038/ni.1836 · Cited by 1,513 · see citing works
Microglial Dysfunction and Defective β-Amyloid Clearance Pathways in Aging Alzheimer's Disease Mice
Hickman, S. E., Allison, E. K., & El Khoury, J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.0616-08.2008 · Cited by 1,329 · cited 1× · see citing works
“inhibit Aβ uptake [35].”
Regulation of innate immune responses in the brain
Rivest, S. (2009) · Nature Reviews Immunology · doi:10.1038/nri2565 · Cited by 843 · see citing works
The role of microglia in amyloid clearance from the AD brain
Lee, C. Y. D., & Landreth, G. E. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0433-4 · Cited by 701 · see citing works
Tuning inflammation and immunity by chemokine sequestration: decoys and more
Mantovani, A., Bonecchi, R., & Locati, M. (2006) · Nature Reviews Immunology · doi:10.1038/nri1964 · Cited by 481 · see citing works
Shaftel, S. S., Kyrkanides, S., Olschowka, J. A., Miller, J.-N. H., Johnson, R. E., & O’Banion, M. K. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31450 · Cited by 433 · see citing works
Lyons, A., Downer, E. J., Crotty, S., Nolan, Y. M., Mills, K. H. G., & Lynch, M. A. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.1781-07.2007 · Cited by 258 · see citing works
Chakrabarty, P., Ceballos-Diaz, C., Beccard, A., Janus, C., Dickson, D., Golde, T. E., & Das, P. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903382 · Cited by 206 · see citing works
Self-citationNSAIDs and incident Alzheimer’s disease. The Rotterdam study
In ’t Veld, B. A., Launer, L. J., Hoes, A. W., Ott, A., Hofman, A., Breteler, M. M. B., & Stricker, B. H. C. (1998) · Neurobiology of Aging · doi:10.1016/s0197-4580(98)00096-7 · Cited by 145 · see citing works
IL-4-Induced Selective Clearance of Oligomeric β-Amyloid Peptide1–42 by Rat Primary Type 2 Microglia
Shimizu, E., Kawahara, K., Kajizono, M., Sawada, M., & Nakayama, H. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.9.6503 · Cited by 143 · see citing works
BRI2 (ITM2b) Inhibits A Deposition In Vivo
Kim, J., Miller, V. M., Levites, Y., West, K. J., Zwizinski, C. W., Moore, B. D., Troendle, F. J., Bann, M., Verbeeck, C., Price, R. W., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0891-08.2008 · Cited by 113 · cited 3× · see citing works
“AAV1 viruses expressing mIL-4 or EGFP, under the control of the cytomegalovirus enhancer/chicken β actin promoter were generated as described previously [19].”
MethodSelf-citationGolde, T. E., & Miller, V. M. (2009) · Alzheimer's Research & Therapy · doi:10.1186/alzrt5 · Cited by 98 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 35
- Cameron B Landreth GE Inflammation, microglia, and Alzheimer's disease Neurobiol Dis 2010 37 503 509 10.1016/j.nbd.2009.10.006 19833208 PMC2823849 · DOI
- Wyss-Coray T Loike JD Brionne TC Lu E Anankov R Yan F Silverstein SC Husemann J Adult mouse astrocytes degrade amyloid-beta in vitro and in situ Nat Med 2003 9 453 457 10.1038/nm838 12612547 · DOI · Paper page
- Brown MA Hural J Functions of IL-4 and control of its expression Crit Rev Immunol 1997 17 1 32 10.1615/CritRevImmunol.v17.i1.10 9034722 · DOI
- Kiyota T Okuyama S Swan RJ Jacobsen MT Gendelman HE Ikezu T CNS expression of anti-inflammatory cytokine interleukin-4 attenuates Alzheimer's disease-like pathogenesis in APP + PS1 bigenic mice FASEB J 2010 24 3093 3102 10.1096/fj.10-155317 20371618 PMC2909296 · DOI · Paper page
- Butovsky O Koronyo-Hamaoui M Kunis G Ophir E Landa G Cohen H Schwartz M Glatiramer acetate fights against Alzheimer's disease by inducing dendritic-like microglia expressing insulin-like growth factor 1 Proc Natl Acad Sci U S A 2006 103 11784 11789 10.1073/pnas.0604681103 16864778 PMC1544247 · DOI · Paper page
- Soria JA Arroyo DS Gaviglio EA Rodriguez-Galan MC Wang JM Iribarren P Interleukin 4 induces the apoptosis of mouse microglial cells by a caspase-dependent mechanism Neurobiol Dis 2011 43 616 624 10.1016/j.nbd.2011.05.010 21624466 PMC3138887 · DOI
- Nolan Y Maher FO Martin DS Clarke RM Brady MT Bolton AE Mills KH Lynch MA Role of interleukin-4 in regulation of age-related inflammatory changes in the hippocampus J Biol Chem 2005 280 9354 9362 15615726
- 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 10.1111/j.1471-4159.2006.04370.x 17250684 · DOI
- Chakrabarty P Jansen-West K Beccard A Ceballos-Diaz C Levites Y Verbeeck C Zubair AC Dickson D Golde TE Das P Massive gliosis induced by interleukin-6 suppresses A{beta} deposition in vivo: evidence against inflammation as a driving force for amyloid deposition FASEB J 2009 24 548 559 19825975 PMC3083918
- Chakrabarty P Herring A Ceballos-Diaz C Das P Golde TE Hippocampal expression of murine TNFalpha results in attenuation of amyloid deposition in vivo Mol Neurodegener 2011 6 16 10.1186/1750-1326-6-16 21324189 PMC3050766 · DOI · Paper page
- El Khoury J Toft M Hickman SE Means TK Terada K Geula C Luster AD Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease Nat Med 2007 13 432 438 10.1038/nm1555 17351623 · DOI · Paper page
- Richard KL Filali M Prefontaine P Rivest S Toll-like receptor 2 acts as a natural innate immune receptor to clear amyloid beta 1–42 and delay the cognitive decline in a mouse model of Alzheimer's disease J Neurosci 2008 28 5784 5793 10.1523/JNEUROSCI.1146-08.2008 18509040 PMC6670789 · DOI · Paper page
- Town T Laouar Y Pittenger C Mori T Szekely CA Tan J Duman RS Flavell RA Blocking TGF-beta-Smad2/3 innate immune signaling mitigates Alzheimer-like pathology Nat Med 2008 14 681 687 18516051 PMC2649699
- Boissonneault V Filali M Lessard M Relton J Wong G Rivest S Powerful beneficial effects of macrophage colony-stimulating factor on beta-amyloid deposition and cognitive impairment in Alzheimer's disease Brain 2009 132 1078 1092 19151372
- 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 16341263 PMC1307561
- Chishti MA Yang DS Janus C Phinney AL Horne P Pearson J Strome R Zuker N Loukides J French J Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695 J Biol Chem 2001 276 21562 21570 10.1074/jbc.M100710200 11279122 · DOI · Paper page
- Harris FM Brecht WJ Xu Q Tesseur I Kekonius L Wyss-Coray T Fish JD Masliah E Hopkins PC Scearce-Levie K Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer's disease-like neurodegeneration and behavioral deficits in transgenic mice Proc Natl Acad Sci U S A 2003 100 10966 10971 10.1073/pnas.1434398100 12939405 PMC196910 · DOI · Paper page
- Nixon RA Autophagy, amyloidogenesis and Alzheimer disease J Cell Sci 2007 120 4081 4091 10.1242/jcs.019265 18032783 · DOI · Paper page
- Ni Cheallaigh C Keane J Lavelle EC Hope JC Harris J Autophagy in the immune response to tuberculosis: clinical perspectives Clin Exp Immunol 2011 164 291 300 10.1111/j.1365-2249.2011.04381.x 21438870 PMC3087924 · DOI
- Mandrekar S Jiang Q Lee CY Koenigsknecht-Talboo J Holtzman DM Landreth GE Microglia mediate the clearance of soluble Abeta through fluid phase macropinocytosis J Neurosci 2009 29 4252 4262 10.1523/JNEUROSCI.5572-08.2009 19339619 PMC3034143 · DOI · Paper page
- Harris J De Haro SA Master SS Keane J Roberts EA Delgado M Deretic V T helper 2 cytokines inhibit autophagic control of intracellular Mycobacterium tuberculosis Immunity 2007 27 505 517 10.1016/j.immuni.2007.07.022 17892853 · DOI
- Moscat J Diaz-Meco MT p62 at the crossroads of autophagy, apoptosis, and cancer Cell 2009 137 1001 1004 10.1016/j.cell.2009.05.023 19524504 PMC3971861 · DOI · Paper page
- Naert G Laflamme N Rivest S Toll-like receptor 2-independent and MyD88-dependent gene expression in the mouse brain J Innate Immun 2009 1 480 493 10.1159/000225990 20375605 · DOI
- Herber DL Mercer M Roth LM Symmonds K Maloney J Wilson N Freeman MJ Morgan D Gordon MN Microglial activation is required for Abeta clearance after intracranial injection of lipopolysaccharide in APP transgenic mice J Neuroimmune Pharmacol 2007 2 222 231 10.1007/s11481-007-9069-z 18040847 · DOI
- Bolmont T Haiss F Eicke D Radde R Mathis CA Klunk WE Kohsaka S Jucker M Calhoun ME Dynamics of the microglial/amyloid interaction indicate a role in plaque maintenance J Neurosci 2008 28 4283 4292 10.1523/JNEUROSCI.4814-07.2008 18417708 PMC3844768 · DOI · Paper page
- Liu Y Walter S Stagi M Cherny D Letiembre M Schulz-Schaeffer W Heine H Penke B Neumann H Fassbender K LPS receptor (CD14): a receptor for phagocytosis of Alzheimer's amyloid peptide Brain 2005 128 1778 1789 10.1093/brain/awh531 15857927 · DOI
- Majumdar A Cruz D Asamoah N Buxbaum A Sohar I Lobel P Maxfield FR Activation of microglia acidifies lysosomes and leads to degradation of Alzheimer amyloid fibrils Mol Biol Cell 2007 18 1490 1496 10.1091/mbc.E06-10-0975 17314396 PMC1838985 · DOI · Paper page
- Paresce DM Ghosh RN Maxfield FR Microglial cells internalize aggregates of the Alzheimer's disease amyloid beta-protein via a scavenger receptor Neuron 1996 17 553 565 10.1016/S0896-6273(00)80187-7 8816718 · DOI · Paper page
- Colton CA Mott RT Sharpe H Xu Q Van Nostrand WE Vitek MP Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD J Neuroinflammation 2006 3 27 10.1186/1742-2094-3-27 17005052 PMC1609108 · DOI · Paper page
- Sonnen JA Larson EB Walker RL Haneuse S Crane PK Gray SL Breitner JC Montine TJ Nonsteroidal anti-inflammatory drugs are associated with increased neuritic plaques Neurology 2010 75 1203 1210 10.1212/WNL.0b013e3181f52db1 20811000 PMC3013492 · DOI
- Wyss-Coray T Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat Med 2006 12 1005 1015 16960575
- Amor S Puentes F Baker D van der Valk P Inflammation in neurodegenerative diseases. Immunology 2010 129 154 169 PMC2814458 20561356
- Koenigsknecht-Talboo J Landreth GE Microglial phagocytosis induced by fibrillar beta-amyloid and IgGs are differentially regulated by proinflammatory cytokines J Neurosci 2005 25 8240 8249 10.1523/JNEUROSCI.1808-05.2005 16148231 PMC6725530 · DOI · Paper page
- Ong CT Sedy JR Murphy KM Kopan R Notch and presenilin regulate cellular expansion and cytokine secretion but cannot instruct Th1/Th2 fate acquisition PLoS One 2008 3 e2823 10.1371/journal.pone.0002823 18665263 PMC2474705 · DOI
- Lee J Chan SL Mattson MP Adverse effect of a presenilin-1 mutation in microglia results in enhanced nitric oxide and inflammatory cytokine responses to immune challenge in the brain Neuromolecular Med 2002 2 29 45 10.1385/NMM:2:1:29 12230303 · DOI
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Ly, P. T. T., Wu, Y., Zou, H., Wang, R., Zhou, W., Kinoshita, A., Zhang, M., Yang, Y., Cai, F., Woodgett, J., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64516 · Cited by 442 · see citing works
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- Authors
- Chakrabarty, P., Tianbai, L., Herring, A., Ceballos-Diaz, C., Das, P., & Golde, T. E.
- Affiliations
- University of Florida (US)
- Mayo Clinic (US)
- Corresponding author
- Golde, Todd E
- Venue
- Molecular Neurodegeneration
- Published
- 2012-07-29
- Volume
- 7
- Issue
- 1
- Pages
- 36-36
- ISSN
- 1750-1326 (ISSN-L)
- PMC
- PMC3441281
- OpenAlex
- W2138274802
- Cited by
- 116
- References
- 13
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 7 · 2022: 11 · 2021: 10 · 2020: 8 · 2019: 9 · 2018: 15 · 2017: 10 · 2016: 11 · 2015: 15 · 2014: 4 · 2013: 3 · 2012: 1
- FWCI
- 4.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Neurodegeneration (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Florida Digital Collections (University of Florida) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- American Health Assistance Foundation
- National Institutes of Health
- National Institute on Aging (R01 AG18454, P01AG025531, R01AG018454, R01AG029886, R01AG29886, P01AG25531)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- IL-4, Alzheimer's disease, amyloid-beta deposition, hippocampus, anti-inflammatory cytokines, neuroinflammation, M2 macrophage phenotype, astrocytes, APP transgenic mice, TgCRND8 mice, AAV gene delivery, innate immunity
- MeSH terms
- Alzheimer Disease, Animals, Astrocytes, Hippocampus, Mice, Transgenic, Interleukin-4, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Microglia, Mice, Plaque, Amyloid
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