Intracerebral microinjection of interleukin-4/interleukin-13 reduces β-amyloid accumulation in the ipsilateral side and improves cognitive deficits in young amyloid precursor protein 23 mice

Kawahara, K.; Suenobu, M.; Yoshida, A.; Koga, K.; Hyodo, A.; Ohtsuka, H.; Kuniyasu, A.; Tamamaki, N.; Sugimoto, Y.; Nakayama, H.

doi:10.1016/j.neuroscience.2012.01.049

Cited by 113Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsNeurological Disease Mechanisms and Treatments

Intracerebral microinjection of interleukin-4/interleukin-13 reduces β-amyloid accumulation in the ipsilateral side and improves cognitive deficits in young amyloid precursor protein 23 mice

Kawahara, K., Suenobu, M., Yoshida, A., Koga, K., Hyodo, A., Ohtsuka, H., Kuniyasu, A., Tamamaki, N. +2 more·2012·Neuroscience

DOI 10.1016/j.neuroscience.2012.01.049

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Abstract

We previously reported that the anti-inflammatory cytokine interleukin (IL)-4 induced selective clearance of oligomeric β-amyloid (Aβ(1-42)) in rat primary type 2 microglial cells. For the present study, we investigated whether IL-4 and IL-13 could activate microglial cells to induce Aβ clearance in vivo and improve cognitive deficits in APP23 mice, which are amyloid precursor protein transgenic mice. We administered an intracerebral microinjection of a mixture of IL-4 and IL-13 or of saline vehicle into one hemisphere of APP23 mice and their wild-type littermates, 4.5 and 9 months old, after which we evaluated the effects of these treatments on spatial learning and memory by Morris Water Maze test and on accumulated amounts of Aβ. The cytokine injection significantly improved memory deficits of 4.5-month-old APP23 mice, but did not do so in 9-month-old APP23 mice, even though similar Aβ reductions were observed in both age groups of APP23 mice in the ipsilateral neocortex. The cytokine injection improved memory impairment of 9-month-old wild-type (WT) mice in the probe trial. Immunohistochemical analysis of the 4.5-month-old APP23 mice revealed the presence of increased numbers of microglial cells at 2 days after the cytokine injection. In addition to induced CD36 expression in the activated microglia, increased expression of neprilysin, mainly in neurons, suggested that the cytokines improved the cognitive deficits via degradation and clearance of intra- and extraneuronal Aβ peptides, of buffer-extractable nonplaque form. Double immunostaining also revealed that most of the activated microglia had the M2-like phenotype. This unique mechanism of IL-4/IL-13-induced clearance of Aβ may provide an additional strategy to prevent and/or cure Alzheimer's disease at early stage.

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Interleukin-4 and interleukin-13 induce clearance of β-amyloid and improve memory in transgenic mice.
“Taken together, interleukin-4 and interleukin-13 induce clearance of β-amyloid and improve memory in transgenic mice.47”
From Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease (2015) · cites this paper as [47]

The mouse brain in stereotaxic coordinates
Konsman, J. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(03)00088-x · Cited by 16,796 · see citing works
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859 · see citing works
Developments of a water-maze procedure for studying spatial learning in the rat
Morris, R. (1984) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(84)90007-4 · Cited by 7,180 · see citing works
Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes
MANTOVANI, A., SOZZANI, S., LOCATI, M., ALLAVENA, P., & SICA, A. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(02)02302-5 · Cited by 5,528 · see citing works
Morris water maze: procedures for assessing spatial and related forms of learning and memory
Vorhees, C. V., & Williams, M. T. (2006) · Nature Protocols · doi:10.1038/nprot.2006.116 · Cited by 4,629 · see citing works
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514 · see citing works
Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis
Kayed, R., Head, E., Thompson, J. L., McIntire, T. M., Milton, S. C., Cotman, C. W., & Glabe, C. G. (2003) · Science · doi:10.1126/science.1079469 · Cited by 4,064 · see citing works
Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse
Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., et al. (1999) · Nature · doi:10.1038/22124 · Cited by 3,160 · see citing works
Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific Aβ monoclonals: Evidence that an initially deposited species is Aβ42(43)
Iwatsubo, T., Odaka, A., Suzuki, N., Mizusawa, H., Nukina, N., & Ihara, Y. (1994) · Neuron · doi:10.1016/0896-6273(94)90458-8 · Cited by 1,774 · see citing works
The role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661 · see citing works
Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology
Sturchler-Pierrat, C., Abramowski, D., Duke, M., Wiederhold, K.-H., Mistl, C., Rothacher, S., Ledermann, B., Bürki, K., Frey, P., Paganetti, P. A., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.24.13287 · Cited by 1,507 · 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
“The reason for this finding has been suggested to be, in part, the inhibition of their phagocytic ability by a chronic inflammatory environment (Koenigsknecht-Talboo and Landreth, 2005; Hickman et al., 2008).”
1α,25-Dihydroxyvitamin D3 Has a Direct Effect on Naive CD4+ T Cells to Enhance the Development of Th2 Cells
Boonstra, A., Barrat, F. J., Crain, C., Heath, V. L., Savelkoul, H. F. J., & O’Garra, A. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.9.4974 · Cited by 1,125 · see citing works
The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease
Youssef, S., Stüve, O., Patarroyo, J. C., Ruiz, P. J., Radosevich, J. L., Hur, E. M., Bravo, M., Mitchell, D. J., Sobel, R. A., Steinman, L., et al. (2002) · Nature · doi:10.1038/nature01158 · Cited by 1,098 · see citing works
Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease
El Khoury, J., Toft, M., Hickman, S. E., Means, T. K., Terada, K., Geula, C., & Luster, A. D. (2007) · Nature Medicine · doi:10.1038/nm1555 · Cited by 915 · see citing works
Regulation of learning and memory by meningeal immunity: a key role for IL-4
Derecki, N. C., Cardani, A. N., Yang, C. H., Quinnies, K. M., Crihfield, A., Lynch, K. R., & Kipnis, J. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20091419 · Cited by 800 · see citing works
Aβ Immunotherapy Leads to Clearance of Early, but Not Late, Hyperphosphorylated Tau Aggregates via the Proteasome
Oddo, S., Billings, L., Kesslak, J. P., Cribbs, D. H., & LaFerla, F. M. (2004) · Neuron · doi:10.1016/j.neuron.2004.07.003 · Cited by 780 · see citing works
Other Functions, Other Genes
Goerdt, S., & Orfanos, C. E. (1999) · Immunity · doi:10.1016/s1074-7613(00)80014-x · Cited by 678 · see citing works
Spherical aggregates of β-amyloid (amylospheroid) show high neurotoxicity and activate tau protein kinase I/glycogen synthase kinase-3β
Hoshi, M. M., Sato, M., Matsumoto, S., Noguchi, A., Yasutake, K., Yoshida, N., & Sato, K. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1237107100 · Cited by 494 · see citing works
Apolipoprotein E is essential for amyloid deposition in the APP V717F transgenic mouse model of Alzheimer's disease
Bales, K. R., Verina, T., Cummins, D. J., Du, Y., Dodel, R. C., Saura, J., Fishman, C. E., DeLong, C. A., Piccardo, P., Petegnief, V., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.15233 · Cited by 486 · see citing works
Microglial Phagocytosis Induced by Fibrillar β-Amyloid and IgGs Are Differentially Regulated by Proinflammatory Cytokines
Koenigsknecht-Talboo, J., & Landreth, G. E. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1808-05.2005 · Cited by 477 · see citing works
Inflammation, autotoxicity and Alzheimer disease
McGeer, P. L. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00289-5 · Cited by 474 · see citing works
The microglial "activation" continuum: from innate to adaptive responses
Town, T., Nikolic, V., & Tan, J. (2005) · Journal of Neuroinflammation · doi:10.1186/1742-2094-2-24 · Cited by 456 · see citing works
Th2 cytokines and asthma — Interleukin-4: its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists
Steinke, J. W., & Borish, L. (2001) · Respiratory Research · doi:10.1186/rr40 · Cited by 445 · see citing works
The inflammatory macrophage: a story of Jekyll and Hyde
Duffield, J. S. (2002) · Clinical Science · doi:10.1042/cs1040027 · Cited by 441 · see citing works
Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD.
(2006) · Journal of Neuroinflammation · doi:10.1186/1742-2094-3-27 · Cited by 393 · see citing works
Glatiramer acetate fights against Alzheimer’s disease by inducing dendritic-like microglia expressing insulin-like growth factor 1
Butovsky, O., Koronyo-Hamaoui, M., Kunis, G., Ophir, E., Landa, G., Cohen, H., & Schwartz, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604681103 · Cited by 388 · see citing works
Somatostatin regulates brain amyloid β peptide Aβ42 through modulation of proteolytic degradation
Saito, T., Iwata, N., Tsubuki, S., Takaki, Y., Takano, J., Huang, S.-M., Suemoto, T., Higuchi, M., & Saido, T. C. (2005) · Nature Medicine · doi:10.1038/nm1206 · Cited by 361 · see citing works
Attenuation of neuroinflammation and Alzheimer's disease pathology by liver x receptors
Zelcer, N., Khanlou, N., Clare, R., Jiang, Q., Reed-Geaghan, E. G., Landreth, G. E., Vinters, H. V., & Tontonoz, P. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701096104 · Cited by 358 · see citing works
Essential role of neocortical acetylcholine in spatial memory
Winkler, J., Suhr, S. T., Gage, F. H., Thal, L. J., & Fisher, L. J. (1995) · Nature · doi:10.1038/375484a0 · Cited by 311 · see citing works
Nasal administration of amyloid-beta peptide decreases cerebral amyloid burden in a mouse model of Alzheimer's disease.
Weiner, H. L., Lemere, C. A., Maron, R., Spooner, E. T., Grenfell, T. J., Mori, C., Issazadeh‐Navikas, S., Hancock, W. W., & Selkoe, D. J. (2000) · PubMed · Cited by 310 · see citing works
Age‐dependent cognitive decline in the APP23 model precedes amyloid deposition
Dam, D. V., D’Hooge, R., Staufenbiel, M., Ginneken, C. J. V., Meir, F. V., & Deyn, P. P. D. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02444.x · Cited by 297 · see citing works
Retinoic acids exert direct effects on T cells to suppress Th1 development and enhance Th2 development via retinoic acid receptors
Iwata, M. (2003) · International Immunology · doi:10.1093/intimm/dxg101 · Cited by 294 · see citing works
A Dynamic Relationship between Intracellular and Extracellular Pools of Aβ
Oddo, S., Caccamo, A., Smith, I. F., Green, K. N., & LaFerla, F. M. (2006) · The American Journal of Pathology · doi:10.2353/ajpath.2006.050593 · Cited by 261 · see citing works
IL-4, IL-10 and IL-13 modulate Aβ(1–42)-induced cytokine and chemokine production in primary murine microglia and a human monocyte cell line
Szczepanik, A. M. (2001) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(00)00404-5 · Cited by 243 · see citing works
Lipopolysaccharide causes deficits in spatial learning in the watermaze but not in BDNF expression in the rat dentate gyrus
Shaw, K. N. (2001) · Behavioural Brain Research · doi:10.1016/s0166-4328(01)00232-7 · Cited by 240 · see citing works
The inflammatory macrophage: a story of Jekyll and Hyde
Duffield, J. S. (2003) · Clinical Science · doi:10.1042/cs20020240 · Cited by 238 · see citing works
Intratumoral administration of recombinant circularly permuted interleukin-4-Pseudomonas exotoxin in patients with high-grade glioma.
Rand, R. W., Kreitman, R. J., Patronas, N., Varricchio, F. E., Pastan, I. H., & Puri, R. K. (2000) · PubMed · Cited by 222 · see citing works
Coinduction of Nitric-oxide Synthase and Arginase I in Cultured Rat Peritoneal Macrophages and Rat Tissues in Vivo by Lipopolysaccharide
Sonoki, T., Nagasaki, A., Gotoh, T., Takiguchi, M., Takeya, M., Matsuzaki, H., & Mori, M. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.6.3689 · Cited by 217 · see citing works
Neuroprotective role of IL-4 against activated microglia.
Chao, C., Molitor, T. W., & Hu, S. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.3.1473 · Cited by 213 · see citing works
CNS expression of anti‐inflammatory cytokine interleukin‐4 attenuates Alzheimer's disease‐like pathogenesis in APP+PS1 bigenic mice
Kiyota, T., Okuyama, S., Swan, R. J., Jacobsen, M. T., Gendelman, H. E., & Ikezu, T. (2010) · The FASEB Journal · doi:10.1096/fj.10-155317 · Cited by 212 · see citing works
Role of Interleukin-4 in Regulation of Age-related Inflammatory Changes in the Hippocampus
Nolan, Y. M., Maher, F. O., Martin, D. S. D., Clarke, R. M., Brady, M. T., Bolton, A. E., Mills, K. H. G., & Lynch, M. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m412170200 · Cited by 210 · see citing works
T-Cells in Alzheimer's Disease
Town, T., Tan, J., Flavell, R. A., & Mullan, M. (2005) · NeuroMolecular Medicine · doi:10.1385/nmm:7:3:255 · Cited by 183 · see citing works
Selective ablation of bone marrow‐derived dendritic cells increases amyloid plaques in a mouse Alzheimer's disease model
Butovsky, O., Kunis, G., Koronyo‐Hamaoui, M., & Schwartz, M. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05652.x · Cited by 167 · see citing works
Butovsky, O. et al. Glatiramer acetate fights against Alzheimer's disease by inducing dendritic-like microglia expressing insulin-like growth factor 1. Proc. Natl Acad. Sci. USA 103, 11784-11789
Butovsky, O., Koronyo‐Hamaoui, M., Kunis, G., Ophir, E., Landa, G., Cohen, H., & Schwartz, M. (2006) · Cited by 144 · 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
Self-citation
Neurobiology of schizophrenia
Pearlson, G. D. (2000) · Annals of Neurology · doi:10.1002/1531-8249(200010)48:4 · Cited by 133 · see citing works
Aβ-specific Th2 cells provide cognitive and pathological benefits to Alzheimer's mice without infiltrating the CNS
Cao, C., Arendash, G. W., Dickson, A., Mamcarz, M. B., Lin, X., & Ethell, D. W. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.12.015 · Cited by 130 · see citing works
Synaptic Activity Reduces Intraneuronal Aβ, Promotes APP Transport to Synapses, and Protects against Aβ-Related Synaptic Alterations
Tampellini, D., Rahman, N., Gallo, E. F., Huang, Z., Dumont, M., Capetillo-Zarate, E., Ma, T., Zheng, R., Lu, B., Nanus, D. M., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.2292-09.2009 · Cited by 127 · see citing works
Morphine directs T cells toward Th2 differentiation
Roy, S., Balasubramanian, S., Sumandeep, S., Charboneau, R., Wang, J., Melnyk, D. L., Beilman, G. J., Vatassery, R., & Barke, R. A. (2001) · Surgery · doi:10.1067/msy.2001.116033 · Cited by 113 · see citing works
Intracellular Accumulation of Insoluble, Newly Synthesized Aβn-42 in Amyloid Precursor Protein-transfected Cells That Have Been Treated with Aβ1–42
Yang, A. J., Chandswangbhuvana, D., Shu, T., Henschen, A., & Glabe, C. G. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.29.20650 · Cited by 108 · see citing works
Cytokine-Mediated Inhibition of Fibrillar Amyloid-β Peptide Degradation by Human Mononuclear Phagocytes
Yamamoto, M., Kiyota, T., Walsh, S. M., Liu, J., Kipnis, J., & Ikezu, T. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.6.3877 · Cited by 100 · see citing works
Interleukin-4 induces proliferation and activation of microglia but suppresses their induction of class II major histocompatibility complex antigen expression
Suzumura, A., Sawada, M., Itoh, Y., & Marunouchi, T. (1994) · Journal of Neuroimmunology · doi:10.1016/0165-5728(94)90031-0 · Cited by 93 · see citing works
Aβ Internalization by Neurons and Glia
Mohamed, A., & Chaves, E. (2011) · International Journal of Alzheimer s Disease · doi:10.4061/2011/127984 · Cited by 91 · see citing works
A Pivotal Role for Interleukin-4 in Atorvastatin-associated Neuroprotection in Rat Brain
Clarke, R. M., Lyons, A., O'Connell, F., Deighan, B. F., Barry, C. E., Anyakoha, N., Nicolaou, A., & Lynch, M. A. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m707442200 · Cited by 85 · see citing works
Electrophysiological studies on the hippocampus and prefrontal cortex assessing the effects of amyloidosis in amyloid precursor protein 23 transgenic mice
Roder, S., Danober, L., Pozza, M. F., Lingenhoehl, K., Wiederhold, K., & Olpe, H. R. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00381-6 · Cited by 72 · see citing works
Reduced Th1 and enhanced Th2 immunity after immunization with Alzheimer's β-amyloid1–42
Town, T., Vendrame, M., Patel, A., Poetter, D., DelleDonne, A., Mori, T., Smeed, R., Crawford, F., Klein, T., Tan, J., et al. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00307-7 · Cited by 72 · see citing works
CB1 and CB2 Cannabinoid Receptors Mediate Different Aspects of Delta-9-Tetrahydrocannabinol (THC)-Induced T Helper Cell Shift Following Immune Activation by Legionella Pneumophila Infection
Newton, C. A., Chou, P.-J., Perkins, I., & Klein, T. (2008) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-008-9126-2 · Cited by 62 · see citing works
Neurofibrillary degeneration and cell loss in the nucleus basalis in comparison to cortical Alzheimer pathology
Cullen, K. M., & Halliday, G. M. (1998) · Neurobiology of Aging · doi:10.1016/s0197-4580(98)00066-9 · Cited by 59 · see citing works
Selective vulnerability of different types of commissural neurons for amyloid -protein-induced neurodegeneration in APP23 mice correlates with dendritic tree morphology
Capetillo-Zarate, E., Staufenbiel, M., Abramowski, D., Haass, C., Escher, A., Stadelmann, C., Yamaguchi, H., Wiestler, O. D., & Thal, D. R. (2006) · Brain · doi:10.1093/brain/awl176 · Cited by 45 · see citing works
Oral Administration of Synthetic Retinoid Am80 (Tamibarotene) Decreases Brain .BETA.-Amyloid Peptides in APP23 Mice
Kawahara, K., Nishi, K., Suenobu, M., Ohtsuka, H., Maeda, A., Nagatomo, K., Kuniyasu, A., Staufenbiel, M., Nakagomi, M., Shudo, K., et al. (2009) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.32.1307 · Cited by 38 · see citing works
Self-citation
Specific uptake of Aβ1-40 in rat brain occurs in astrocyte, but not in microglia
Matsunaga, W., Shirokawa, T., & Isobe, K. (2003) · Neuroscience Letters · doi:10.1016/s0304-3940(03)00240-4 · Cited by 36 · see citing works

Flagged first, then by citations

1 of the 64 references couldn’t be matched to a known paper.

Sorted by citations

Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases
Tang, Y., & Le, W. (2016) · Molecular Neurobiology · doi:10.1007/s12035-014-9070-5 · Cited by 2,190 · see citing works
Neuroinflammation and M2 Microglia: The Good, the Bad, and the Inflamed
Cherry, J. D., Olschowka, J. A., & O’Banion, M. K. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-98 · Cited by 1,748 · see citing works
Alternatively activated microglia and macrophages in the central nervous system
Franco, R., & Fernández‐Suárez, D. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.05.003 · Cited by 650 · see citing works
Interleukin-4 Is Essential for Microglia/Macrophage M2 Polarization and Long-Term Recovery After Cerebral Ischemia
Liu, X., Liu, J., Zhao, S., Zhang, H., Cai, W., Cai, M., Ji, X., Leak, R. K., Gao, Y., Chen, J., et al. (2016) · Stroke · doi:10.1161/strokeaha.115.012079 · Cited by 405 · see citing works
Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition
Pasciuto, E., Burton, O. T., Roca, C. P., Lagou, V., Rajan, W. D., Theys, T., Mancuso, R., Tito, R. Y., Kouser, L., Callaerts-Vegh, Z., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.026 · Cited by 368 · see citing works
Microglia Phenotypes in Aging and Neurodegenerative Diseases
Wendimu, M. Y., & Hooks, S. B. (2022) · Cells · doi:10.3390/cells11132091 · Cited by 336 · see citing works
Modulation of learning and memory by cytokines: Signaling mechanisms and long term consequences
Donzis, E. J., & Tronson, N. C. (2014) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2014.08.008 · Cited by 254 · see citing works
Microglial Aβ Receptors in Alzheimer’s Disease
Yu, Y., & Ye, R. D. (2015) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-014-0101-6 · Cited by 247 · see citing works
Omega-3 Fatty Acids Enhance Phagocytosis of Alzheimer's Disease-Related Amyloid-β 42 by Human Microglia and Decrease Inflammatory Markers
Hjorth, E., Zhu, M., Toro, V. C., Vedin, I., Palmblad, J. E. W., Cederholm, T., Freund‐Levi, Y., Irving, G. F., Wahlund, L., Basun, H., et al. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-130131 · Cited by 229 · see citing works
Inflammatory Cytokines and Alzheimer’s Disease: A Review from the Perspective of Genetic Polymorphisms
Su, F., Bai, F., & Zhang, Z. (2016) · Neuroscience Bulletin · doi:10.1007/s12264-016-0055-4 · Cited by 221 · see citing works
Role of microglial m1/m2 polarization in relapse and remission of psychiatric disorders and diseases
Nakagawa, Y., & Chiba, K. (2014) · Pharmaceuticals · doi:10.3390/ph7121028 · Cited by 215 · see citing works
Inflammation in the Neurocircuitry of Obsessive-Compulsive Disorder
Attwells, S., Setiawan, E., Wilson, A. A., Rusjan, P., Mizrahi, R., Miler, L., Xu, C., Richter, M. A., Kahn, A., Kish, S. J., et al. (2017) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2017.1567 · Cited by 209 · see citing works
Galactic Cosmic Radiation Leads to Cognitive Impairment and Increased Aβ Plaque Accumulation in a Mouse Model of Alzheimer’s Disease
Cherry, J. D., Liu, B., Frost, J. L., Lemere, C. A., Williams, J. P., Olschowka, J. A., & O’Banion, M. K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0053275 · Cited by 198 · see citing works
Exploiting microglial and peripheral immune cell crosstalk to treat Alzheimer’s disease
Dionisio-Santos, D. A., Olschowka, J. A., & O’Banion, M. K. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1453-0 · Cited by 184 · see citing works
Human umbilical cord mesenchymal stem cell-derived neuron-like cells rescue memory deficits and reduce amyloid-beta deposition in an AβPP/PS1 transgenic mouse model
Yang, H., Xie, Z., Wei, L. F., Yang, H. N., Yang, S. N., Zhu, Z., Wang, P., Zhao, C., & Bi, J. Z. (2013) · Stem Cell Research & Therapy · doi:10.1186/scrt227 · Cited by 166 · see citing works
Microglia activation states and cannabinoid system: Therapeutic implications
Mecha, M., Carrillo-Salinas, F. J., Feliú, A., Mestre, L., & Guaza, C. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.06.011 · Cited by 160 · see citing works
Arginase 1+ microglia reduce Aβ plaque deposition during IL-1β-dependent neuroinflammation
Cherry, J. D., Olschowka, J. A., & O’Banion, M. K. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0411-8 · Cited by 152 · see citing works
Microglial polarization: novel therapeutic mechanism against Alzheimer’s disease
Yao, K., & Zu, H. (2019) · Inflammopharmacology · doi:10.1007/s10787-019-00613-5 · Cited by 146 · see citing works
O -GlcNAcylation ameliorates the pathological manifestations of Alzheimer’s disease by inhibiting necroptosis
Park, J., Ha, H.-J., Chung, E. S., Baek, S. H., Cho, Y., Kim, H. K., Han, J., Sul, J. H., Lee, J., Kim, E., et al. (2021) · Science Advances · doi:10.1126/sciadv.abd3207 · Cited by 139 · see citing works
Neuroimmunology of the Interleukins 13 and 4
Mori, S., Maher, P. A., & Conti, B. (2016) · Brain Sciences · doi:10.3390/brainsci6020018 · Cited by 127 · see citing works
Targeting innate immunity for neurodegenerative disorders of the central nervous system
Andreasson, K. I., Bachstetter, A. D., Colonna, M., Ginhoux, F., Holmes, C., Lamb, B., Landreth, G., Lee, D. C., Low, D., Lynch, M. A., et al. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13667 · Cited by 126 · see citing works
Treadmill exercise induces age-related changes in aversive memory, neuroinflammatory and epigenetic processes in the rat hippocampus
Lovatel, G. A., Elsner, V. R., Bertoldi, K., Vanzella, C., Moysés, F. D. S., Vizuete, A. F. K., Spindler, C. D. F., Cechinel, L. R., Netto, C. A., Muotri, A. R., et al. (2013) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.01.007 · Cited by 126 · see citing works
Exercise as a potential modulator of inflammation in patients with Alzheimer's disease measured in cerebrospinal fluid and plasma
Jensen, C. S., Bahl, J. M. C., Østergaard, L. B., Høgh, P., Wermuth, L., Heslegrave, A., Zetterberg, H., Heegaard, N. H. H., Hasselbalch, S. G., & Simonsen, A. H. (2019) · Experimental Gerontology · doi:10.1016/j.exger.2019.04.003 · Cited by 120 · see citing works
Basic Pharmacological and Structural Evidence for Class A G-Protein-Coupled Receptor Heteromerization
Franco, R., Martínez‐Pinilla, E., Lanciego, J. L., & Navarro, G. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00076 · Cited by 120 · see citing works
Mesenchymal stem cells enhance α-synuclein clearance via M2 microglia polarization in experimental and human parkinsonian disorder
Park, H.-J., Oh, S. H., Kim, H., Jung, Y. J., & Lee, P. H. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1605-6 · Cited by 111 · see citing works
Systemic inflammatory regulators and risk of Alzheimer’s disease: a bidirectional Mendelian-randomization study
Yeung, C. H. C., & Schooling, C. M. (2020) · International Journal of Epidemiology · doi:10.1093/ije/dyaa241 · Cited by 111 · see citing works
Anti-inflammatory IL-10 administration rescues depression-associated learning and memory deficits in mice
Worthen, R. J., Zighelboim, S. S. G., Jaramillo, C., & Beurel, E. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01922-1 · Cited by 109 · see citing works
Activation of the α7 nicotinic receptor promotes lipopolysaccharide-induced conversion of M1 microglia to M2.
Zhang, Q., Lu, Y., Bian, H., Guo, L., & Zhu, H. (2017) · PubMed Central · Cited by 106 · see citing works
Transgenic Increase in n-3/n-6 Fatty Acid Ratio Protects Against Cognitive Deficits Induced by an Immune Challenge through Decrease of Neuroinflammation
Delpech, J.-C., Madore, C., Joffre, C., Aubert, A., Kang, J. X., Nadjar, A., & Layé, S. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.196 · Cited by 98 · see citing works
Activation of murine microglial N9 cells is attenuated through cannabinoid receptor CB2 signaling
Ma, L., Jia, J., Liu, X., Bai, F., Wang, Q., & Xiong, L. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.01.073 · Cited by 90 · see citing works
IL-13 Ameliorates Neuroinflammation and Promotes Functional Recovery after Traumatic Brain Injury
Miao, W., Zhao, Y., Huang, Y., Chen, D., Luo, C., Su, W., & Gao, Y. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1900909 · Cited by 86 · see citing works
IL12/23 p40 Inhibition Ameliorates Alzheimer's Disease-Associated Neuropathology and Spatial Memory in SAMP8 Mice
Tan, M., Yu, J., Jiang, T., Zhu, X., Guan, H., & Tan, L. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-131148 · Cited by 80 · see citing works
M2 Macrophage Transplantation Ameliorates Cognitive Dysfunction in Amyloid-β-Treated Rats Through Regulation of Microglial Polarization
Zhu, D., Yang, N., Liu, Y., Zheng, J., Ji, C., & Zuo, P. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-151090 · Cited by 78 · see citing works
Macrophage efferocytosis in health and disease
Razi, S., Khojini, J. Y., Kargarijam, F., Panahi, S., Tahershamsi, Z., Tajbakhsh, A., & Hayat, S. M. G. (2023) · Cell Biochemistry and Function · doi:10.1002/cbf.3780 · Cited by 80 · see citing works
Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease
Lalli, M. A., Bettcher, B. M., Arcila, M. L., Garcia, G., Guzman, C., Madrigal, L., Ramirez, L., Acosta-Uribe, J., Baena, A., Wojta, K. J., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.131 · Cited by 73 · see citing works
Interleukin-13 immune gene therapy prevents CNS inflammation and demyelination via alternative activation of microglia and macrophages: Modulation of CNS Inflammation by Interkeukin-13
Guglielmetti, C., Le Blon, D., Santermans, E., Salas-Perdomo, A., Daans, J., De Vocht, N., Shah, D., Hoornaert, C., Praet, J., Peerlings, J., et al. (2016) · Glia · doi:10.1002/glia.23053 · Cited by 76 · see citing works
MFG-E8 Selectively Inhibited Aβ-Induced Microglial M1 Polarization via NF-κB and PI3K-Akt Pathways
Shi, X., Cai, X., Di, W., Li, J., Xu, X., Zhang, A., Qi, W., Zhou, Z., & Fang, Y. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0255-y · Cited by 76 · see citing works
Results and insights from a phase I clinical trial of Lomecel‐B for Alzheimer's disease
Brody, M., Agronin, M., Herskowitz, B., Bookheimer, S. Y., Small, G. W., Hitchinson, B., Ramdas, K. N., Wishard, T. J., McInerney, K., Vellas, B. J., et al. (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12651 · Cited by 72 · see citing works
Central and Peripheral Administration of Antisense Oligonucleotide Targeting Amyloid-β Protein Precursor Improves Learning and Memory and Reduces Neuroinflammatory Cytokines in Tg2576 (AβPPswe) Mice
Farr, S. A., Erickson, M. A., Niehoff, M. L., Banks, W. A., & Morley, J. E. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-131883 · Cited by 72 · see citing works
Naringenin promotes microglial M2 polarization and Aβ degradation enzyme expression
Yang, Z., Kuboyama, T., & Tohda, C. (2019) · Phytotherapy Research · doi:10.1002/ptr.6305 · Cited by 69 · see citing works
Neuroprotective modulation of microglia effector functions following priming with interleukin 4 and 13: current limitations in understanding their mode-of-action
Quarta, A., Berneman, Z. N., & Ponsaerts, P. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.03.023 · Cited by 67 · see citing works
Neuromodulation of Glial Function During Neurodegeneration
Stevenson, R., Samokhina, E., Rossetti, I., Morley, J. W., & Buskila, Y. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00278 · Cited by 68 · see citing works
The role of microglia in the development of neurodegeneration
Saitgareeva, A. R., Bulygin, K. V., Фанилевич, Г. И., Beylerli, O., & Ахмадеева, Л. Р. (2020) · Neurological Sciences · doi:10.1007/s10072-020-04468-5 · Cited by 67 · see citing works
Type 2 immunity in the brain and brain borders
Mamuladze, T., & Kipnis, J. (2023) · Cellular and Molecular Immunology · doi:10.1038/s41423-023-01043-8 · Cited by 65 · see citing works
USP8 protects against lipopolysaccharide-induced cognitive and motor deficits by modulating microglia phenotypes through TLR4/MyD88/NF-κB signaling pathway in mice
Zhao, J., Bi, W., Zhang, J., Xiao, S., Zhou, R., Tsang, C. K., Lu, D., & Zhu, L. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.04.052 · Cited by 64 · see citing works
Review: Experimental manipulations of microglia in mouse models of <scp>A</scp>lzheimer's pathology: activation reduces amyloid but hastens tau pathology
Lee, D. C., Rizer, J., Hunt, J. B., Selenica, M. ‐. B., Gordon, M. N., & Morgan, D. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12002 · Cited by 57 · see citing works
Interleukin-4 affects microglial autophagic flux
Tang, R.-H., Qi, R.-Q., & Liu, H.-Y. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.255975 · Cited by 56 · see citing works
Cooperative Therapeutic Action of Retinoic Acid Receptor and Retinoid X Receptor Agonists in a Mouse Model of Alzheimer's Disease
Kawahara, K., Suenobu, M., Ohtsuka, H., Kuniyasu, A., Sugimoto, Y., Nakagomi, M., Fukasawa, H., Shudo, K., & Nakayama, H. (2014) · Journal of Alzheimer's Disease · doi:10.3233/jad-132720 · Cited by 51 · see citing works
Self-citation
OAB-14, a bexarotene derivative, improves Alzheimer's disease-related pathologies and cognitive impairments by increasing β-amyloid clearance in APP/PS1 mice
Yuan, C., Guo, X., Zhou, Q., Du, F., Jiang, W., Zhou, X., Liu, P., Chi, T., Ji, X., Gao, J., et al. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.10.028 · Cited by 48 · see citing works
Differential Associations of IL-4 With Hippocampal Subfields in Mild Cognitive Impairment and Alzheimer’s Disease
Boccardi, V., Westman, E., Pelini, L., Lindberg, O. E., Muehlboeck, J., Simmons, A., Tarducci, R., Floridi, P., Chiarini, P., Soininen, H. S., et al. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00439 · Cited by 42 · see citing works
Neuroinflammation in Alzheimer’s Disease: Microglia, Molecular Participants and Therapeutic Choices
Wang, H., Shen, Y., Chuang, H.-Y., Chiu, C., Ye, Y., & Zhao, L. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666190503151648 · Cited by 42 · see citing works
Elucidating the influence of environmentally relevant toxic metal mixture on molecular mechanisms involved in the development of neurodegenerative diseases: In silico toxicogenomic data-mining
Živančević, K., Baralić, K., Jorgovanović, D., Djordjević, A. B., Ćurčić, M., Miljaković, E. A., Antonijević, B., Bulat, Z., & Đukić-Ćosić, D. (2021) · Environmental Research · doi:10.1016/j.envres.2021.110727 · Cited by 39 · see citing works
Prostaglandin E2 Receptor Subtype 2 Regulation of Scavenger Receptor CD36 Modulates Microglial Aβ42 Phagocytosis
Li, X., Melief, E. J., Postupna, N. O., Montine, K. S., Keene, C. D., & Montine, T. J. (2014) · American Journal Of Pathology · doi:10.1016/j.ajpath.2014.09.016 · Cited by 37 · see citing works
Interleukin-4 and Interleukin-13 Exacerbate Neurotoxicity of Prothrombin Kringle-2 in Cortex In Vivo via Oxidative Stress
Jeong, J. Y., Chung, Y. C., & Jin, B. K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20081927 · Cited by 37 · see citing works
Reciprocal modulation of C / EBP ‐α and C / EBP ‐β by IL ‐13 in activated microglia prevents neuronal death
Pan, H. C., Yang, C. N., Hung, Y. W., Lee, W. J., Tien, H., Shen, C. C., Sheehan, J. P., Chou, C., & Sheu, M. (2013) · European Journal of Immunology · doi:10.1002/eji.201343301 · Cited by 36 · see citing works
Reduced TREM2 activation in microglia of patients with Alzheimer's disease
Okuzono, Y., Sakuma, H., Miyakawa, S., Ifuku, M., Lee, J. H., Das, D., Banerjee, A., Zhao, Y., Yamamoto, K., Ando, T., et al. (2021) · FEBS Open Bio · doi:10.1002/2211-5463.13300 · Cited by 31 · see citing works
Increased neutrophils in inflammatory bowel disease accelerate the accumulation of amyloid plaques in the mouse model of Alzheimer’s disease
Kaneko, R., Matsui, A., Watanabe, M., Harada, Y., Kanamori, M., Awata, N., Kawazoe, M., Takao, T., Kobayashi, Y., Kikutake, C., et al. (2023) · Inflammation and Regeneration · doi:10.1186/s41232-023-00257-7 · Cited by 30 · see citing works
Innate immunity in Alzheimer’s disease: the relevance of animal models?
Franco-Bocanegra, D., Nicoll, J. A. R., & Boche, D. (2017) · Journal of Neural Transmission · doi:10.1007/s00702-017-1729-4 · Cited by 31 · see citing works
The role of meningeal populations of type II innate lymphoid cells in modulating neuroinflammation in neurodegenerative diseases
Yeung, S. S.-H., Ho, J. Y. S., & Chang, R. C. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00660-5 · Cited by 29 · see citing works
TREM2 in Alzheimer's disease: Structure, function, therapeutic prospects, and activation challenges
Zgórzyńska, E. (2024) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2024.103917 · Cited by 28 · see citing works
Cytokines and Cytokine Receptors Involved in the Pathogenesis of Alzheimers Disease
Nagae, T., & Araki, K. (2016) · Journal of Clinical & Cellular Immunology · doi:10.4172/2155-9899.1000441 · Cited by 28 · see citing works
Aß Pathology and Neuron–Glia Interactions: A Synaptocentric View
Huffels, C. F. M., Middeldorp, J., & Hol, E. M. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03699-6 · Cited by 27 · see citing works
Single-cell RNA sequencing identifies distinct transcriptomic signatures between PMA/ionomycin- and αCD3/αCD28-activated primary human T cells
Lee, J. H., Lee, B. H., Jeong, S., Joh, C. S.-Y., Nam, H. J., Choi, H. S., Sserwadda, H., Oh, J. W., Park, C., Jin, S., et al. (2023) · Genomics & Informatics · doi:10.5808/gi.23009 · Cited by 21 · see citing works
Association of interleukin-4 genetic polymorphisms with sporadic Alzheimer's disease in Chinese Han population
Li, W., Qian, X., Teng, H., Ding, Y., & Zhang, L. (2014) · Neuroscience Letters · doi:10.1016/j.neulet.2014.01.019 · Cited by 22 · see citing works
Evaluating the Effect of Interleukin-4 in the 3xTg Mouse Model of Alzheimer’s Disease
Dionisio-Santos, D. A., Behrouzi, A., Olschowka, J. A., & O’Banion, M. K. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00441 · Cited by 20 · see citing works
Reciprocal Interplay Between Astrocytes and CD4+ Cells Affects Blood-Brain Barrier and Neuronal Function in Response to β Amyloid
Spampinato, S. F., Merlo, S., Fagone, E., Fruciano, M., Sano, Y., Kanda, T., & Sortino, M. A. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00120 · Cited by 19 · see citing works
Brain interleukins and Alzheimer’s disease
Abdelhamed, H. G., Hassan, A. A., Sakraan, A., Al-Deeb, R. T., Mousa, D. M., Ezz, H. S. A., Noor, N. A., Khadrawy, Y. A., & Radwan, N. M. (2025) · Metabolic Brain Disease · doi:10.1007/s11011-025-01538-5 · Cited by 20 · see citing works
A Computational Exploration of the Molecular Network Associated to Neuroinflammation in Alzheimer’s Disease
Idrissi, F. E., Gressier, B., Devos, D., & Bélarbi, K. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.630003 · Cited by 18 · see citing works
Metabolomic research on the role of interleukin-4 in Alzheimer’s disease
González‐Domínguez, R., García‐Barrera, T., Vitórica, J., & Gómez‐Ariza, J. L. (2015) · Metabolomics · doi:10.1007/s11306-015-0773-z · Cited by 18 · see citing works
Oxygen-glucose deprivation regulates BACE1 expression through induction of autophagy in Neuro-2a/APP695 cells
Chen, R., Zhang, T., Sun, Y.-Y., Sun, Y.-M., Chen, W., Shi, N., Shen, F., Zhang, Y., Liu, K.-Y., & Sun, X.-J. (2015) · Neural Regeneration Research · doi:10.4103/1673-5374.165511 · Cited by 20 · see citing works
Memory decline correlates with increased plasma cytokines in amyloid-beta (1–42) rat model of Alzheimer’s disease
Shallie, O. F., Dallé, E., & Mabandla, M. V. (2020) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2020.107187 · Cited by 17 · see citing works
Early loss of locus coeruleus innervation promotes cognitive and neuropathological changes before amyloid plaque deposition in a transgenic rat model of Alzheimer's disease
Aguilar, L. F., Hall, H., Orciani, C., Foret, M. K., Kovecses, O., Ducatenzeiler, A., & Cuello, A. C. (2022) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12835 · Cited by 16 · see citing works
Interleukin-4 Modulates Neuroinflammation by Inducing Phenotypic Transformation of Microglia Following Subarachnoid Hemorrhage
Wang, J., Wang, L., Wu, Q., Cai, Y., Cui, C., Yang, M., Sun, B., Mao, L., & Wang, Y. (2023) · Inflammation · doi:10.1007/s10753-023-01917-z · Cited by 19 · see citing works
Normal aging, motor neurone disease, and Alzheimer’s disease are characterized by cortical changes in inflammatory cytokines
Tennakoon, A., Katharesan, V., Musgrave, I., Koblar, S. A., Faull, R. L. M., Curtis, M. A., & Johnson, I. (2021) · Journal of Neuroscience Research · doi:10.1002/jnr.24996 · Cited by 17 · see citing works
Intermittent fasting reprograms the brain proteome to prevent synaptic degeneration and cognitive impairment in vascular dementia
Tabassum, N. I., Selvaraji, S., Fan, Y., Lim, V. J. T., Cheng, X., Peng, X., Arora, A., Rajeev, V., Ratcliffe, J., Johnson, C. J., et al. (2025) · Theranostics · doi:10.7150/thno.119422 · Cited by 15 · see citing works
Interleukin-4 Aggravates LPS-Induced Striatal Neurodegeneration In Vivo via Oxidative Stress and Polarization of Microglia/Macrophages
Jang, J., Hong, A., Chung, Y. C., & Jin, B.-K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23010571 · Cited by 15 · see citing works
Extracellular domain of TREM2 possess two distinct ligand recognition sites: Insights from machine-learning guided docking and all-atoms molecular dynamics simulations
Mishra, S., Swain, P. S., Pati, S., & Dehury, B. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e41414 · Cited by 14 · see citing works
Inflammation in the CNS: Understanding Various Aspects of the Pathogenesis of Alzheimer's Disease
Doroszkiewicz, J., Mroczko, P., & Kulczyńska‐Przybik, A. (2021) · Current Alzheimer Research · doi:10.2174/1567205018666211202143935 · Cited by 14 · see citing works
Early treatment with an M1 and sigma-1 receptor agonist prevents cognitive decline in a transgenic rat model displaying Alzheimer-like amyloid pathology
Orciani, C., Carmo, S. D., Foret, M. K., Hall, H., Bonomo, Q., Lavagna, A., Huang, C., & Cuello, A. C. (2023) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2023.09.010 · Cited by 14 · see citing works
The novel monoclonal antibody 9F5 reveals expression of a fragment of GPNMB/osteoactivin processed by furin‐like protease(s) in a subpopulation of microglia in neonatal rat brain
Kawahara, K., Hirata, H., Ohbuchi, K., Nishi, K., Maeda, A., Kuniyasu, A., Yamada, D., Maeda, T., Tsuji, A., Sawada, M., et al. (2016) · Glia · doi:10.1002/glia.23034 · Cited by 14 · see citing works
Self-citation
Neonatal Neurodegeneration in Alzheimer’s Disease Transgenic Mouse Model
Mazi, A. R., Arzuman, A. S., Gürel, B., Şahin, B., Tüzüner, M. B., Ozansoy, M., & Baykal, A. T. (2018) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-170049 · Cited by 13 · see citing works
Bacopa monnieri confers neuroprotection by influencing signaling pathways associated with interleukin 4, 13 and extracellular matrix organization in Alzheimer's disease: A proteomics-based perspective
Palollathil, A., Najar, M. A., Amrutha, S., Pervaje, R., Modi, P. K., & Prasad, T. S. K. (2024) · Neurochemistry International · doi:10.1016/j.neuint.2024.105864 · Cited by 12 · see citing works
Cross-regulation between the nervous system and type 2 immunity
Mroz, N. M., Chiaranunt, P., Molofsky, A. V., & Molofsky, A. B. (2025) · Science Immunology · doi:10.1126/sciimmunol.adp6450 · Cited by 11 · see citing works
Interleukin 13 on Microglia is Neurotoxic in Lipopolysaccharide-injected Striatumin vivo
Hong, A. R., Jang, J. G., Chung, Y. C., Won, S.-Y., & Jin, B. K. (2022) · Experimental Neurobiology · doi:10.5607/en21032 · Cited by 11 · see citing works
Angiostrongylus cantonensis causes cognitive impairments in heavily infected BALB/c and C57BL/6 mice
Jhan, K.-Y., Lai, G.-J., Chang, P.-K., Tang, R.-Y., Cheng, C.-J., Chen, K.-Y., & Wang, L.-C. (2020) · Parasites & Vectors · doi:10.1186/s13071-020-04230-y · Cited by 11 · see citing works
Network Pharmacology Study of Heat‐Clearing and Detoxifying Traditional Chinese Medicine for Alzheimer′s Disease
Li, H., Zhang, X., Gu, L., Wu, N., Zhang, L., Lü, J., & Li, Q. (2020) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2020/7831675 · Cited by 10 · see citing works
Effects of α-Lipoic Acid on Phagocytosis of Oligomeric Beta-Amyloid1–42 in BV-2 Mouse Microglial Cells
Ko, C., Xu, J., Chang, Y.-W. W., Lo, Y.-M. M., Wu, J. S., Huang, W., & Shen, S. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.788723 · Cited by 10 · see citing works
Differentiated Expression Patterns and Phagocytic Activities of Type 1 and 2 Microglia
Haga, A., Takahashi, E., Inomata, Y., Kawahara, K., & Tanihara, H. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-18509 · Cited by 10 · see citing works
Self-citation
Low-dose intranasal deferoxamine modulates memory, neuroinflammation, and the neuronal transcriptome in the streptozotocin rodent model of Alzheimer’s disease
Fine, J. M., Kosyakovsky, J., Bowe, T. T., Faltesek, K. A., STROEBEL, B. M., Abrahante, J. E., Kelly, M. R., Thompson, E. A., Westby, C. M., Robertson, K. M., et al. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1528374 · Cited by 9 · see citing works
Traumatic Brain Injury Accelerates the Onset of Cognitive Dysfunction and Aggravates Alzheimer's-Like Pathology in the Hippocampus by Altering the Phenotype of Microglia in the APP/PS1 Mouse Model
Wu, D., Kumal, J. P. P., Lu, X., Li, Y., Mao, D., Tang, X., Nie, M., Liu, X., Sun, L., Liu, B., et al. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.666430 · Cited by 9 · see citing works
Injury intensifies T cell mediated graft-versus-host disease in a humanized model of traumatic brain injury
Diaz, M. F., Horton, P. D., Kumar, A., Livingston, M. K., Mohammadalipour, A., Xue, H., Skibber, M. A., Ewere, A., Furman, N. E. T., Aroom, K., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-67723-x · Cited by 9 · see citing works
Interleukin-13 Propagates Prothrombin Kringle-2-Induced Neurotoxicity in Hippocampi In Vivo via Oxidative Stress
Jeong, J. Y., Wi, R., Chung, Y. C., & Jin, B. K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073486 · Cited by 8 · see citing works
The NLRP3-P2X7 Axis and Cytokine Crosstalk in Alzheimer's Disease: Mechanisms, Implications, and Therapeutic Opportunities
Kurmi, S., Doshi, G., & Parab, S. B. (2025) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/0118715273377780250505115039 · Cited by 7 · see citing works
Inhibiting the Cholesterol Storage Enzyme ACAT1/SOAT1 in Aging Apolipoprotein E4 Mice Alters Their Brains’ Inflammatory Profiles
Huynh, T. N. T., Fikse, E. N., Torre, A. L. D. L., Havrda, M. C., Chang, C. C. Y., & Chang, T. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252413690 · Cited by 9 · see citing works
Variations in inflammatory regulators in male patients with chronic schizophrenia associated with psychopathology and cognitive deficits
Guo, T., Chen, L., Luan, L., Yang, M. L., Zhang, X., & Yang, H. (2024) · BMC Psychiatry · doi:10.1186/s12888-024-06288-9 · Cited by 8 · see citing works
Temporary upregulation of anti-inflammatory cytokine IL-13 expression in the brains of CD14 deficient mice in the early stage of prion infection
Hasebe, R., Suzuki, A., Yamasaki, T., & Horiuchi, M. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.10.043 · Cited by 6 · see citing works
Modelling of anti-inflammatory treatment in the Alzheimer disease: optimal regimen and outcome
Hajj, W. E., Pujo-Menjouet, L., Tine, L. M., & Volpert, V. A. (2025) · Bulletin of Mathematical Biology · doi:10.1007/s11538-025-01553-8 · Cited by 3 · see citing works
Differential effects of Huang-Lian-Jie-Du Decoction on Alzheimer’s disease and normal rats
Xu, M., Zhu, Y., Chen, J., Zhong, F., Wang, R., Li, J., Qiao, M., Fan, Y., Ren, P., Chen, M., et al. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1710919 · Cited by 4 · see citing works
Comprehensive investigation of the expression profiles of common long noncoding RNAs during microglial activation
Kim, J., Lee, B., Kim, B. C., Kim, J., Kim, J., & Cho, H. (2023) · Genomics & Informatics · doi:10.5808/gi.22061 · Cited by 4 · see citing works
Reduction in Hippocampal Amyloid-β Peptide (Aβ) Content during Glycine-Proline-Glutamate (Gly-Pro-Glu) Co-Administration Is Associated with Changes in Inflammation and Insulin-like Growth Factor (IGF)-I Signaling
Frago, L. M., Burgos‐Ramos, E., Rodríguez-Pérez, M., Canelles, S., Arilla, E., Argente, J., López, M. G., & Barrios, V. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25115716 · Cited by 3 · see citing works

P4‐337: Reducing Alzheimer's disease beta‐amyloid and cognitive deficits by manipulating il‐12/il‐23 signaling
Obst, J., Prokop, S., Berg, J. V., Miller, K., Kälin, R. E., Cabezas, I. L., Wegner, A., Mair, F., Winter, Y., Becher, B., et al. (2012) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2013.08.118
O1‐04–08: Therapeutic application of anti‐inflammatory cytokines an Abeta‐induced cognitive dysfunction
Ikezu, T., Kiyota, T., Yamamoto, M., Xu, J., Jacobsen, M. T., & Okuyama, S. (2008) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2008.05.245
Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease–like pathology and cognitive decline
vom Berg, J., Prokop, S., Miller, K. R., Obst, J., Kälin, R. E., Lopategui-Cabezas, I., Wegner, A., Mair, F., Schipke, C. G., Peters, O., et al. (2012) · Nature Medicine · doi:10.1038/nm.2965 · Cited by 416 · see citing works
Influence of IL-12 / IL-23 signaling on Alzheimer’s disease β-amyloid pathology
Obst, J. (2017) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-13171 · Cited by 1 · see citing works
O3‐05–08: Amyloid‐β‐responsive Th2 cells reduce microglial activation, reduce serum cytokines, increase plasma amyloid‐β, and improve hippocampal‐dependent memory in APP+PS1 mice
Ethell, D. W., Cao, C., Dickson, A., Mamcarz, M. B., Xiaoyang, L., & Arendash, G. W. (2008) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2008.05.448

Authors: Kawahara, K., Suenobu, M., Yoshida, A., Koga, K., Hyodo, A., Ohtsuka, H., Kuniyasu, A., Tamamaki, N., Sugimoto, Y., & Nakayama, H.
Affiliations: Kumamoto University (JP)
Corresponding author: Nakayama, H.
ORCID: Kawahara, K.
Yoshida, A.
Koga, K.
Kuniyasu, A.
Sugimoto, Y.
Nakayama, H.
Venue: Neuroscience
Publisher: Elsevier BV
Published: 2012-04
Volume: 207
Pages: 243-260
ISSN: 0306-4522 (ISSN-L)
DOI: 10.1016/j.neuroscience.2012.01.049
OpenAlex: W1986944486
Cited by: 113
References: 64
Citations by year: 2026: 2 · 2025: 11 · 2024: 7 · 2023: 10 · 2022: 8 · 2021: 9 · 2020: 15 · 2019: 8 · 2018: 3 · 2017: 3 · 2016: 13 · 2015: 7 · 2014: 10 · 2013: 5 · 2012: 2
FWCI: 5.14
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Neuroscience (publishedVersion)
PubMed (publishedVersion)
Kumamoto University Repository (Kumamoto University) (submittedVersion)
Kumamoto University Repository System (submittedVersion)
Funders: Ministry of Education, Culture, Sports, Science and Technology
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords: IL-4, IL-13, amyloid-beta clearance, APP23 mice, Alzheimer's disease, microglial activation, neprilysin, CD36, spatial learning and memory, cognitive impairment, anti-inflammatory cytokines, early Alzheimer's disease
MeSH terms: Aging, Alzheimer Disease, Animals, Cognition Disorders, Disease Models, Animal, Humans, Injections, Intraventricular, Male, Mice, Inbred C57BL, Mice, Transgenic, Microinjections, Interleukin-4, Amyloid beta-Peptides, Interleukin-13, Mice, Plaque, Amyloid

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Intracerebral microinjection of interleukin-4/interleukin-13 reduces β-amyloid accumulation in the ipsilateral side and improves cognitive deficits in young amyloid precursor protein 23 mice

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