Mechanisms of Mononuclear Phagocyte Recruitment in Alzheimers Disease
Open accessAbstract
Alzheimer's disease (AD) is associated with a significant neuroinflammatory component. Mononuclear phagocytes including monocytes and microglia are the principal cells involved, and they accumulate at perivascular sites of beta-amyloid (Abeta) deposition and in senile plaques. Recent evidence suggests that mononuclear phagocyte accumulation in the AD brain is dependent on chemokines. CCL2, a major monocyte chemokine, is upregulated in the AD brain. Interaction of CCL2 with its receptor CCR2 regulates mononuclear phagocyte accumulation in a mouse model of AD. CCR2 deficiency leads to lower mononuclear phagocyte accumulation and is associated with higher brain Abeta levels, specifically around blood vessels, suggesting that monocytes accumulate at sites of Abeta deposition in an initial attempt to clear these deposits and stop or delay their neurotoxic effects. Indeed, enhancing mononuclear phagocyte accumulation delays progression of AD. Here we review the mechanisms of mononuclear phagocyte accumulation in AD and discuss the potential roles of additional chemokines and their receptors in this process. We also propose a multi-step model for recruitment of mononuclear phagocytes into the brain. The first step involves egress of monocyte/microglial precursors from the bone marrow into the blood. The second step is crossing the blood-brain barrier to the perivascular areas and into the brain parenchyma. The final step includes movement of monocytes/microglia from areas of the brain that lack any amyloid deposition to senile plaques. Understanding the mechanism of recruitment of mononuclear phagocytes to the AD brain is necessary to further understand the role of these cells in the pathogenesis of AD and to identify any potential therapeutic use of these cells for the treatment of this disease.
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CX3CR1 is a chemokine receptor expressed on microglia and a subset of monocytes.
“CX3CR1 is a chemokine receptor expressed on microglia and a subset of monocytes (8, 9).”
From Heterozygous CX3CR1 Deficiency in Microglia Restores Neuronal β-Amyloid Clearance Pathways and Slows Progression of Alzheimer's Like-Disease in PS1-APP Mice (2019) · cites this paper as [8]
The “Chemokines and Accumulation of Mononuclear Phagocytes in AD” section identifies CX3CR1 as the fractalkine receptor, and “Additional Chemokines that may also Control Microglia Accumulation in AD” says it is highly expressed on microglia. The “Recruitment of Monocytes into the AD Brain” section links CX3CR1 to monocyte trafficking, but our copy does not specify that its expression is limited to a subset of monocytes. (LLM, conf=0.84)
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Monitoring of Blood Vessels and Tissues by a Population of Monocytes with Patrolling Behavior
Auffray, C., Fogg, D., Garfa, M., Elain, G., Join-Lambert, O., Kayal, S., Sarnacki, S., Cumano, A., Lauvau, G., & Geissmann, F. (2007) · Science · doi:10.1126/science.1142883 · Cited by 1,973 · see citing works
Serbina, N. V., & Pamer, E. G. (2006) · Nature Immunology · doi:10.1038/ni1309 · Cited by 1,658 · see citing works
Local self-renewal can sustain CNS microglia maintenance and function throughout adult life
Ajami, B., Bennett, J. L., Krieger, C., Tetzlaff, W., & Rossi, F. M. V. (2007) · Nature Neuroscience · doi:10.1038/nn2014 · Cited by 1,643 · see citing works
Control of microglial neurotoxicity by the fractalkine receptor
Cardona, A. E., Pioro, E. P., Sasse, M. E., Kostenko, V., Cardona, S. M., Dijkstra, I. M., Huang, D., Kidd, G., Dombrowski, S., Dutta, R., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1715 · Cited by 1,531 · see citing works
Simard, A. R., Soulet, D., Gowing, G., Julien, J.-P., & Rivest, S. (2006) · Neuron · doi:10.1016/j.neuron.2006.01.022 · Cited by 1,265 · see citing works
Tsou, C.-L., Peters, W., Si, Y., Slaymaker, S., Aslanian, A. M., Weisberg, S. P., Mack, M., & Charo, I. F. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29919 · Cited by 1,152 · see citing works
Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions
Mildner, A., Schmidt, H., Nitsche, M., Merkler, D., Hanisch, U.-K., Mack, M., Heikenwalder, M., Brück, W., Priller, J., & Prinz, M. (2007) · Nature Neuroscience · doi:10.1038/nn2015 · Cited by 1,089 · see citing works
Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice
Eglitis, M. A., & Mezey, É. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.4080 · Cited by 1,015 · see citing works
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
Self-citationMcGeer, P. L., Itagaki, S., Tago, H., & McGeer, E. G. (1987) · Neuroscience Letters · doi:10.1016/0304-3940(87)90696-3 · Cited by 836 · see citing works
Mechanisms of Disease: astrocytes in neurodegenerative disease
Maragakis, N., & Rothstein, J. (2006) · Nature Clinical Practice Neurology · doi:10.1038/ncpneuro0355 · Cited by 834 · see citing works
Inflammatory processes in Alzheimer's disease
Heneka, M. T., & O'Banion, M. K. (2007) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.11.017 · Cited by 782 · see citing works
Fong, A. M., Robinson, L. A., Steeber, D. A., Tedder, T. F., Yoshie, O., Imai, T., & Patel, D. D. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.8.1413 · Cited by 682 · see citing works
Priller, J., Flügel, A., Wehner, T., Boentert, M., Haas, C. A., Prinz, M., Fernández-Klett, F., Prass, K., Bechmann, I., de Boer, B. A., et al. (2001) · Nature Medicine · doi:10.1038/nm1201-1356 · Cited by 637 · see citing works
Microglial response to amyloid plaques in APPsw transgenic mice.
Frautschy, S. A., Yang, F., Irrizarry, M., Hyman, B. T., Saido, T. C., Hsiao, K., & Cole, G. M. (1998) · Europe PMC (PubMed Central) · Cited by 592 · see citing works
Izikson, L., Klein, R. S., Charo, I. F., Weiner, H. L., & Luster, A. D. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.7.1075 · Cited by 584 · see citing works
Chemokines and Their Receptors: Drug Targets in Immunity and Inflammation
Viola, A., & Luster, A. D. (2007) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.48.121806.154841 · Cited by 583 · see citing works
Decreased atherosclerosis in CX3CR1–/– mice reveals a role for fractalkine in atherogenesis
Lesnik, P., Haskell, C. A., & Charo, I. F. (2003) · Journal of Clinical Investigation · doi:10.1172/jci15555 · Cited by 487 · see citing works
CD36 Mediates the Innate Host Response to β-Amyloid
El Khoury, J. B., Moore, K. J., Means, T. K., Leung, J., Terada, K., Toft, M., Freeman, M. W., & Luster, A. D. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021546 · Cited by 483 · see citing works
Self-citationDecreased Atherosclerotic Lesion Formation in CX3CR1/Apolipoprotein E Double Knockout Mice
Combadière, C., Potteaux, S., Gao, J.-L., Esposito, B., Casanova, S., Lee, E. J., Debré, P., Tedgui, A., Murphy, P. M., & Mallat, Z. (2003) · Circulation · doi:10.1161/01.cir.0000057548.68243.42 · Cited by 476 · 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
Blocking TGF-β–Smad2/3 innate immune signaling mitigates Alzheimer-like pathology
Town, T., Laouar, Y., Pittenger, C., Mori, T., Szekely, C. A., Tan, J., Duman, R. S., & Flavell, R. A. (2008) · Nature Medicine · doi:10.1038/nm1781 · Cited by 422 · see citing works
Hawkes, C. A., & McLaurin, J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805453106 · Cited by 397 · see citing works
Charlier, C., Nielsen, K., Daou, S., Brigitte, M., Chretien, F., & Dromer, F. (2009) · Infection and Immunity · doi:10.1128/iai.01065-08 · Cited by 362 · see citing works
Simard, A. R., & Rivest, S. (2004) · The FASEB Journal · doi:10.1096/fj.04-1517fje · Cited by 354 · see citing works
Malm, T. M., Koistinaho, M., Pärepalo, M., Vatanen, T., Ooka, A., Karlsson, S., & Koistinaho, J. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.09.009 · Cited by 301 · see citing works
Ccr5 But Not Ccr1 Deficiency Reduces Development of Diet-Induced Atherosclerosis in Mice
Braunersreuther, V., Zernecke, A., Arnaud, C., Liehn, E. A., Steffens, S., Shagdarsuren, E., Bidzhekov, K., Burger, F., Pelli, G., Luckow, B., et al. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000253886.44609.ae · Cited by 287 · see citing works
Hematopoietic origin of microglial and perivascular cells in brain
Hess, D. C., Abe, T., Hill, W., Martin-Studdard, A., Carothers, J., Masuya, M., Fleming, P. A., Drake, C. J., & Ogawa, M. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2003.11.005 · Cited by 281 · see citing works
Frackowiak, J., Wisniewski, H. M., Wegiel, J., Merz, G. S., Iqbal, K., & Wang, K. C. (1992) · Acta Neuropathologica · doi:10.1007/bf00227813 · Cited by 276 · see citing works
Chemokines/chemokine receptors in the central nervous system and Alzheimer's disease
Xia, M., & Hyman, B. T. (1999) · Journal of NeuroVirology · doi:10.3109/13550289909029743 · Cited by 269 · see citing works
Sokolova, A., Hill, M. D., Rahimi, F., Warden, L. A., Halliday, G. M., & Shepherd, C. E. (2009) · Brain Pathology · doi:10.1111/j.1750-3639.2008.00188.x · Cited by 249 · see citing works
ISHIZUKA, K., KIMURA, T., IGATA‐YI, R., KATSURAGI, S., TAKAMATSU, J., & MIYAKAWA, T. (1997) · Psychiatry and Clinical Neurosciences · doi:10.1111/j.1440-1819.1997.tb02375.x · Cited by 245 · see citing works
Morphologic association between microglia and senile plaque amyloid in Alzheimer's disease
Perlmutter, L. S., Barron, E., & Chui, H. C. (1990) · Neuroscience Letters · doi:10.1016/0304-3940(90)90748-x · Cited by 240 · see citing works
Zachariae, C. O. C., Anderson, A. O., Thompson, H. L., Appella, E., Mantovani, A., Oppenheim, J. J., & Matsushima, K. (1990) · The Journal of Experimental Medicine · doi:10.1084/jem.171.6.2177 · Cited by 238 · see citing works
Microglial Recruitment, Activation, and Proliferation in Response to Primary Demyelination
Remington, L. T., Babcock, A. A., Zehntner, S. P., & Owens, T. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.060783 · Cited by 234 · see citing works
Town, T., Bai, F., Wang, T., Kaplan, A. T., Qian, F., Montgomery, R. R., Anderson, J. F., Flavell, R. A., & Fikrig, E. (2009) · Immunity · doi:10.1016/j.immuni.2008.11.012 · Cited by 217 · see citing works
The microglial phagocytic role with specific plaque types in the Alzheimer disease brain
D’Andrea, M. R., Cole, G. M., & Ard, M. D. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.12.026 · Cited by 215 · see citing works
Weber, C., Alon, R., Moser, B., & Springer, T. A. (1996) · The Journal of Cell Biology · doi:10.1083/jcb.134.4.1063 · Cited by 214 · see citing works
Pathogenesis of Cerebral <i>Cryptococcus neoformans</i> Infection after Fungemia
Chrétien, F., Lortholary, O., Kansau, I., Neuville, S., Gray, F., & Dromer, F. (2002) · The Journal of Infectious Diseases · doi:10.1086/341564 · Cited by 201 · see citing works
Boisvert, W. A., Rose, D. M., Johnson, K. A., Fuentes, M. E., Lira, S. A., Curtiss, L. K., & Terkeltaub, R. A. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.040748 · Cited by 189 · see citing works
Djukic, M. (2006) · Brain · doi:10.1093/brain/awl206 · Cited by 186 · see citing works
From bone marrow to microglia: barriers and avenues
Davoust, N., Vuaillat, C., Androdias, G., & Nataf, S. (2008) · Trends in Immunology · doi:10.1016/j.it.2008.01.010 · Cited by 173 · see citing works
Mechanisms of microglia accumulation in Alzheimer’s disease: therapeutic implications
Khoury, J. E., & Luster, A. D. (2008) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2008.08.004 · Cited by 171 · see citing works
Self-citationGene expression profiling of amyloid beta peptide-stimulated human post-mortem brain microglia
Walker, D. G. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00306-2 · Cited by 155 · see citing works
Chemokines and chemokine receptors: multipurpose players in neuroinflammation.
Ransohoff, R., Liu, L.-P., & Cardona, A. (2007) · International review of neurobiology · doi:10.1016/s0074-7742(07)82010-1 · Cited by 151 · see citing works
Zernecke, A., Liehn, E. A., Gao, J., Kuziel, W. A., Murphy, P. M., & Weber, C. (2006) · Blood · doi:10.1182/blood-2005-09-3922 · Cited by 148 · see citing works
Sievers, J., Parwaresch, R. M., & Wottge, H. ‐. (1994) · Glia · doi:10.1002/glia.440120402 · Cited by 138 · see citing works
Stalder, M., Deller, T., Staufenbiel, M., & Jucker, M. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00209-3 · Cited by 118 · see citing works
Phagocytosis of ?/A4 amyloid fibrils of the neuritic neocortical plaques
Wisniewski, H. M., Barcikowska, M., & Kida, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00310142 · Cited by 109 · see citing works
Neuronal Structure is Altered by Amyloid Plaques
Spires‐Jones, T. L., & Hyman, B. T. (2004) · Reviews in the Neurosciences · doi:10.1515/revneuro.2004.15.4.267 · Cited by 107 · see citing works
Early and Rapid Engraftment of Bone Marrow-Derived Microglia in Scrapie
Priller, J., Prinz, M., Heikenwälder, M. F., Zeller, N., Schwarz, P., Heppner, F. L., & Aguzzi, A. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2275-06.2006 · Cited by 89 · see citing works
Kokovay, E., & Cunningham, L. A. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.01.023 · Cited by 88 · see citing works
Chemokine regulation of atherosclerosis
Barlic, J., & Murphy, P. M. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.1206761 · Cited by 79 · see citing works
Neuropathology of Alzheimer's Disease
Mott, R. T., & Hulette, C. M. (2005) · Neuroimaging Clinics of North America · doi:10.1016/j.nic.2005.09.003 · Cited by 68 · see citing works
Neuropathology of Alzheimer's Disease
Gómez‐Isla, T., Spires‐Jones, T. L., de Calignon, A., & Hyman, B. T. (2008) · Handbook of clinical neurology · doi:10.1016/s0072-9752(07)01222-5 · Cited by 52 · see citing works
Prat, E., Baron, P., Meda, L., Scarpini, E. A., Galimberti, D., Ardolino, G., Catania, A. P., & Scarlato, G. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)00966-6 · Cited by 44 · see citing works
The use of chemokine antagonists in EAE models
Proudfoot, A. E. I., Souza, A. L. S., & Muzio, V. (2008) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2008.04.007 · Cited by 32 · see citing works
Imamoto, K. (1981) · PubMed · Cited by 30 · see citing works
Ling, E. (1979) · Archivum histologicum japonicum · doi:10.1679/aohc1950.42.41 · Cited by 18 · see citing works
Flagged first, then by citations
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Sorted by citations
Microglia in neurodegeneration
Hickman, S., Izzy, S., Sen, P., Morsett, L., & El Khoury, J. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0242-x · Cited by 1,710 · see citing works
Self-citationDealing with danger in the CNS: the response of the immune system to injury
Gadani, S. P., Walsh, J. T., Lukens, J. R., & Kipnis, J. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.019 · Cited by 342 · see citing works
Microglia–blood vessel interactions: a double-edged sword in brain pathologies
Dudvarski Stankovic, N., Teodorczyk, M., Ploen, R., Zipp, F., & Schmidt, M. H. H. (2016) · Acta Neuropathologica · doi:10.1007/s00401-015-1524-y · Cited by 301 · see citing works
Magdalinou, N. K., Paterson, R. W., Schott, J. M., Fox, N. C., Mummery, C. J., Blennow, K., Bhatia, K. P., Morris, H. R., Giunti, P., Warner, T. T., et al. (2015) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2014-309562 · Cited by 250 · 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
Xu, X.-E., Liu, L., Wang, Y.-C., Wang, C.-T., Zheng, Q., Liu, Q.-X., Li, Z.-F., Bai, X.-J., & Liu, X.-H. (2019) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2019.05.038 · Cited by 211 · see citing works
de Pablos, R. M., Herrera, A. J., Espinosa-Oliva, A. M., Sarmiento, M., Muñoz, M. F., Machado, A., & Venero, J. L. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-34 · Cited by 201 · see citing works
Mahmoudi, M., Quinlan-Pluck, F., Monopoli, M. P., Sheibani, S., Vali, H., Dawson, K. A., & Lynch, I. (2012) · ACS Chemical Neuroscience · doi:10.1021/cn300196n · Cited by 159 · see citing works
MacPherson, K. P., Sompol, P. M., Kannarkat, G. T., Chang, J., Sniffen, L. J., Wildner, M., Norris, C. M., & Tansey, M. G. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2017.02.010 · Cited by 158 · see citing works
Koronyo, Y., Salumbides, B. C., Sheyn, J., Pelissier, L., Li, S., Ljubimov, V., Moyseyev, M., Daley, D., Fuchs, D.-T., Pham, M., et al. (2015) · Brain · doi:10.1093/brain/awv150 · Cited by 153 · see citing works
Cai, Q., Li, Y., & Pei, G. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0839-0 · Cited by 154 · see citing works
Morari, J., Anhê, G. F., do Nascimento, L. F. R., de Moura, R. F., Razolli, D. S., Solon, C., Guadagnini, D., de Souza, G. F. P., Mattos, A. H. B., Tobar, N., et al. (2014) · Diabetes · doi:10.2337/db13-1495 · Cited by 147 · see citing works
CC and CXC chemokines are pivotal mediators of cerebral injury in ischaemic stroke
Viviani, G. L., Dallegri, F., Quercioli, A., Veneselli, E., Mach, F., Mirabelli-Badenier, M., Braunersreuther, V., & Montecucco, F. (2010) · Thrombosis and Haemostasis · doi:10.1160/th10-10-0662 · Cited by 144 · see citing works
Inflammatory monocytes and the pathogenesis of viral encephalitis
Terry, R. L., Getts, D. R., Deffrasnes, C., van Vreden, C., Campbell, I. L., & King, N. J. C. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-270 · Cited by 134 · see citing works
Tao, L., Liu, Q., Zhang, F., Fu, Y., Zhu, X. D., Weng, X., Han, H., Huang, Y., Suo, Y., Chen, L., et al. (2021) · Light Science & Applications · doi:10.1038/s41377-021-00617-3 · Cited by 133 · see citing works
Telomere length is age-dependent and reduced in monocytes of Alzheimer patients
Hochstrasser, T., Marksteiner, J., & Humpel, C. (2011) · Experimental Gerontology · doi:10.1016/j.exger.2011.11.012 · Cited by 132 · see citing works
A Complex Proinflammatory Role for Peripheral Monocytes in Alzheimer's Disease
Saresella, M., Marventano, I., Calabrese, E., Piancone, F., Rainone, V., Gatti, A. V., Alberoni, M., Nemni, R., & Clerici, M. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-131160 · Cited by 121 · see citing works
Bernstein, K. E., Koronyo, Y., Salumbides, B. C., Sheyn, J., Pelissier, L., Lopes, D. H. J., Shah, K. H., Bernstein, E. A., Fuchs, D.-T. S., Yu, J. J.-Y., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci66541 · Cited by 117 · see citing works
Guedes, J. R., Lao, T., Cardoso, A. L., & El Khoury, J. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00549 · Cited by 115 · see citing works
Amiri, H., Saeidi, K., Borhani, P., Manafirad, A., Ghavami, M., & Zerbi, V. (2013) · ACS Chemical Neuroscience · doi:10.1021/cn4001582 · Cited by 114 · see citing works
Microglial interactions with the neurovascular system in physiology and pathology
Zhao, X., Eyo, U. B., Murugan, M., & Wu, L. (2018) · Developmental Neurobiology · doi:10.1002/dneu.22576 · Cited by 109 · see citing works
Systemic and CNS Inflammation Crosstalk: Implications for Alzheimer’s Disease
Paouri, E., & Georgopoulos, S. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666190321154618 · Cited by 108 · see citing works
Mietelska‐Porowska, A., & Wojda, U. (2017) · Journal of Immunology Research · doi:10.1155/2017/4626540 · Cited by 107 · see citing works
Schütt, T., Helboe, L., Pedersen, L. Ø., Waldemar, G., Berendt, M., & Pedersen, J. T. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-151085 · Cited by 105 · see citing works
Kiyota, T., Gendelman, H. E., Weir, R. A., Higgins, E. E., Zhang, G., & Jain, M. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.08.009 · Cited by 90 · see citing works
Ataka, K., Asakawa, A., Nagaishi, K., Kaimoto, K., Sawada, A., Hayakawa, Y., Tatezawa, R., Inui, A., & Fujimiya, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081744 · Cited by 89 · see citing works
The Potential Role of Chemokines in Alzheimer’s Disease Pathogenesis
Azizi, G., Hossein‐Khannazer, N., & Mirshafiey, A. (2014) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317513518651 · Cited by 89 · see citing works
Hickman, S. E., Allison, E. K., Coleman, U., Kingery-Gallagher, N. D., & El Khoury, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02780 · Cited by 80 · see citing works
Self-citationKnockout of ccr2 alleviates photoreceptor cell death in a model of retinitis pigmentosa
Guo, C., Otani, A., Oishi, A., Kojima, H., Makiyama, Y., Nakagawa, S., & Yoshimura, N. (2012) · Experimental Eye Research · doi:10.1016/j.exer.2012.08.013 · Cited by 81 · see citing works
Migration of blood cells to β-amyloid plaques in Alzheimer's disease
Hohsfield, L. A., & Humpel, C. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.03.002 · Cited by 79 · see citing works
Anti-Aggregating Effect of the Naturally Occurring Dipeptide Carnosine on Aβ1-42 Fibril Formation
Aloisi, A., Barca, A., Romano, A., Guerrieri, S., Storelli, C., Rinaldi, R., & Verri, T. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068159 · Cited by 75 · see citing works
The Role of Inflammatory Mediators in the Pathogenesis of Alzheimer’s Disease
Azizi, G., Navabi, S. S., Al-Shukaili, A. K., Seyedzadeh, M. H., Yazdani, R., & Mirshafiey, A. (2015) · Sultan Qaboos University medical journal · doi:10.18295/squmj.2015.15.03.002 · Cited by 72 · see citing works
Bhat, N. R. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06978.x · Cited by 70 · see citing works
Hebron, M., Lonskaya, I., Olopade, P., Selby, S., Pagán, F., & Moussa, C. (2014) · Journal of Clinical & Cellular Immunology · doi:10.4172/2155-9899.1000259 · Cited by 67 · see citing works
Beckmann, N., Gérard, C., Abramowski, D., Cannet, C., & Staufenbiel, M. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.4936-10.2011 · Cited by 65 · see citing works
Zhang, X., Wang, B., O'Callaghan, P. W., Hjertström, E., Jia, J., Gong, F., Zcharia, E., Nilsson, L. N. G., Lannfelt, L., Vlodavsky, I., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-0997-1 · Cited by 65 · see citing works
Th1 Polarization of T Cells Injected into the Cerebrospinal Fluid Induces Brain Immunosurveillance
Fisher, Y., Strominger, I., Biton, S., Nemirovsky, A., Baron, R., & Monsonego, A. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1301707 · Cited by 64 · see citing works
Lampron, A., Lessard, M., & Rivest, S. (2012) · Cell Transplantation · doi:10.3727/096368911x593154 · Cited by 65 · see citing works
Ge, S., Shrestha, B., Paul, D., Keating, C. E., Cone, R. E., Guglielmotti, A., & Pachter, J. S. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-171 · Cited by 64 · see citing works
Pan-SHIP1/2 inhibitors promote microglia effector functions essential for CNS homeostasis
Pedicone, C., Fernandes, S., Dungan, O. M., Dormann, S. M., Viernes, D. R., Adhikari, A. A., Choi, L. B., De Jong, E. P., Chisholm, J. D., & Kerr, W. G. (2020) · Journal of Cell Science · doi:10.1242/jcs.238030 · Cited by 61 · see citing works
Hypothalamic mitochondrial abnormalities occur downstream of inflammation in diet-induced obesity
Carraro, R. S., de Souza, G. F. P., Solon, C., Razolli, D. S., Chausse, B., Barbizan, R., Victorio, S. C. D. S., & Velloso, L. A. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.07.029 · Cited by 61 · see citing works
The Chemerin Receptor CMKLR1 is a Functional Receptor for Amyloid-β Peptide
Lei, P., Yu, Y., Liu, J., Li, S., He, H., Cheng, N., & Ye, R. D. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-141227 · Cited by 59 · see citing works
Apolipoprotein E isoform‐dependent microglia migration
Cudaback, E., Li, X., Montine, K. S., Montine, T. J., & Keene, C. D. (2011) · The FASEB Journal · doi:10.1096/fj.10-176891 · Cited by 58 · see citing works
Oussini, H. E., Bayer, H., Scekic‐Zahirovic, J., Vercruysse, P., Sinniger, J., Dirrig‐Grosch, S., Dieterle, S., Echaniz‐Laguna, A., Larmet, Y., Müller, K., et al. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1534-4 · Cited by 56 · see citing works
Monocytes and Alzheimer’s disease
Feng, Y., Li, L., & Sun, X. (2011) · Neuroscience Bulletin · doi:10.1007/s12264-011-1205-3 · Cited by 54 · see citing works
Dwellers and Trespassers: Mononuclear Phagocytes at the Borders of the Central Nervous System
Ivan, D. C., Walthert, S., Berve, K., Steudler, J., & Locatelli, G. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.609921 · Cited by 53 · see citing works
Importance of GPCR-Mediated Microglial Activation in Alzheimer’s Disease
Haque, M. E., Kim, I., Jakaria, M., Akther, M., & Choi, D. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00258 · Cited by 55 · see citing works
Li, S., Hayden, E. Y., Garcia, V. J., Fuchs, D.-T. S., Sheyn, J., Daley, D. A., Rentsendorj, A., Torbati, T., Black, K. L., Rutishauser, U., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00049 · Cited by 48 · see citing works
The Roles of Monocyte and Monocyte‐Derived Macrophages in Common Brain Disorders
Zhao, M., Tuo, H., Wang, S., & Zhao, L. (2020) · BioMed Research International · doi:10.1155/2020/9396021 · Cited by 46 · see citing works
Leptin, neuroinflammation and obesity
Dragano, N. R. V., Haddad-Tovolli, R., & Velloso, L. A. (2017) · Frontiers of hormone research · doi:10.1159/000452908 · Cited by 45 · see citing works
Hydroxytyrosol Interference with Inflammaging via Modulation of Inflammation and Autophagy
Velotti, F., & Bernini, R. (2023) · Nutrients · doi:10.3390/nu15071774 · Cited by 47 · see citing works
Umhau, J. C., Schwandt, M. L., Solomon, M. G., Yuan, P., Nugent, A. C., Zarate, C. A., Drevets, W. C., Hall, S. D., George, D. T., & Heilig, M. A. (2014) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.12367 · Cited by 45 · see citing works
Human glutaminyl cyclase: Structure, function, inhibitors and involvement in Alzheimer’s disease
Dileep, K. V., & Zhang, K. Y. J. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104342 · Cited by 43 · see citing works
Yagura, K., Ohtaki, H., Tsumuraya, T., Sato, A., Miyamoto, K., Kawada, N., Suzuki, K., Nakamura, M., Kanzaki, K., Dohi, K., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0230080 · Cited by 30 · see citing works
Lemche, E., Killick, R., Mitchell, J., Caton, P., Choudhary, P., & Howard, J. K. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106485 · Cited by 42 · see citing works
Fiala, M., Terrando, N., & Dalli, J. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150367 · Cited by 41 · see citing works
Glial cells and adaptive immunity in frontotemporal dementia with tau pathology
Hartnell, I. J., Blum, D. L., Nicoll, J. A. R., Dorothée, G., & Boche, D. (2020) · Brain · doi:10.1093/brain/awaa457 · Cited by 40 · see citing works
Kawaguchi, M., Yamamoto, T., Kato, Y., Inose, Y., & Shibata, N. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-21 · Cited by 39 · see citing works
MECHANISMS IN ENDOCRINOLOGY: Hypothalamic inflammation and nutrition
ARAUJO, E. P. D., Moraes, J. C., Cintra, D. E., & Velloso, L. A. (2016) · European Journal of Endocrinology · doi:10.1530/eje-15-1207 · Cited by 39 · see citing works
Lopes, J. R. D., Zhang, X., Mayrink, J., Tatematsu, B. K., Guo, L., LeServe, D. S., Abou‐El‐Hassan, H., Rong, F., Dalton, M. J., Oliveira, M. G., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2309221120 · Cited by 38 · see citing works
Sanati, M., Aminyavari, S., Khodagholi, F., Hajipour, M. J., Sadeghi, P., Noruzi, M., Moshtagh, A., Behmadi, H., & Sharifzadeh, M. S. (2021) · NeuroToxicology · doi:10.1016/j.neuro.2021.05.013 · Cited by 35 · see citing works
Immunology meets neuroscience – Opportunities for immune intervention in neurodegenerative diseases
Lynch, M. A., & Mills, K. H. G. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.05.013 · Cited by 33 · see citing works
Xie, X., Li, M.-Z., Yao, E., Gong, S., Xie, J., Gao, W., Xie, Z., Li, Z., Bai, X., Liu, L., et al. (2020) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2020.03.019 · Cited by 30 · see citing works
Kimura, A., Yoshikura, N., Hayashi, Y., & Inuzuka, T. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170519 · Cited by 29 · see citing works
Editorial [Hot topic: Inflammation, Immunity, and Alzheimers Disease (Guest Editor: Terrence Town)]
Town, T. (2010) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152710791012008 · Cited by 27 · see citing works
Maté, I., Cruces, J., Giménez‐Llort, L., & la Fuente, M. D. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-140861 · Cited by 26 · see citing works
Yang, Z., Wang, J., Yu, Y., & Li, Z. (2016) · International Immunopharmacology · doi:10.1016/j.intimp.2016.01.016 · Cited by 25 · see citing works
Lee, E.-H., Han, M., Ha, J., Park, H.-H., Koh, S., Choi, S. H., & Lee, J. (2020) · Aging · doi:10.18632/aging.202206 · Cited by 22 · see citing works
MAJOR BIOACTIVE PROPERTIES OF GANODERMA POLYSACCHARIDES: A REVIEW
Bhat, Z. A., Wani, A. H., War, J. M., & Bhat, M. Y. (2021) · Asian Journal of Pharmaceutical and Clinical Research · doi:10.22159/ajpcr.2021.v14i3.40390 · Cited by 23 · see citing works
Association between Resistin Gene Polymorphisms and Atopic Dermatitis
Banihani, S. A., Abualia, K., Khabour, O. F., & Alzoubi, K. H. (2018) · Biomolecules · doi:10.3390/biom8020017 · Cited by 22 · see citing works
Pathology of Amyloid-β (Aβ) Peptide Peripheral Clearance in Alzheimer’s Disease
Tsoy, A., Umbayev, B. A., Kassenova, A., Kaupbayeva, B., & Askarova, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252010964 · Cited by 23 · see citing works
Multicellular hypothesis for the pathogenesis of Alzheimer's disease
Goetzl, E. J., & Miller, B. L. (2017) · The FASEB Journal · doi:10.1096/fj.201601221r · Cited by 19 · see citing works
Inhibition of hypothalamic leukemia inhibitory factor exacerbates diet-induced obesity phenotype
Fioravante, M., Bombassaro, B., Ramalho, A. F. S., Dragano, N. R. V., Morari, J., Solon, C., Tobar, N., Ramos, C. D., & Velloso, L. A. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0956-9 · Cited by 19 · see citing works
Targeting the pro‐inflammatory factor CCL2 (MCP‐1) with Bindarit for influenza A (H7N9) treatment
Wolf, S., Johnson, S. K., Perwitasari, O., Mahalingam, S., & Tripp, R. A. (2017) · Clinical & Translational Immunology · doi:10.1038/cti.2017.8 · Cited by 18 · see citing works
Xu, Y., Shen, Y., Zhang, X. ‐., Gui, L., Cai, M., Peng, G., Pan, X. ‐., Zhang, J., Gan, D., Li, B., et al. (2020) · European Journal of Neurology · doi:10.1111/ene.14254 · Cited by 18 · see citing works
Differential Chemokine Responses in the Murine Brain Following Lyssavirus Infection
Hicks, D. J., Núñez, A., Banyard, A. C., Williams, A., Ortiz‐Peláez, A., Fooks, A. R., & Johnson, N. (2013) · Journal of Comparative Pathology · doi:10.1016/j.jcpa.2013.04.001 · Cited by 18 · see citing works
Spontaneous Development of Autoimmune Uveitis Is CCR2 Dependent
Chen, Y. F., Zhou, D., Metzger, T. C., Gallup, M., Jeanne, M., Gould, D. B., Anderson, M. S., & McNamara, N. A. (2014) · American Journal Of Pathology · doi:10.1016/j.ajpath.2014.02.024 · Cited by 18 · see citing works
Jahanbani, F., Sing, J., Maynard, R. D., Jahanbani, S., Dafoe, J., Dafoe, W., Jones, N., Wallace, K. J., Rastan, A., Maecker, H. T., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1369295 · Cited by 16 · see citing works
Chemokines in neurodegenerative diseases
Vida, H., Sahar, M., Nikdouz, A., & Hosseini, A. (2024) · Immunology and Cell Biology · doi:10.1111/imcb.12843 · Cited by 17 · see citing works
Liu, S.-H., Gao, H.-W., Gao, C.-Z., Liu, W.-G., & Xing, D.-G. (2017) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-017-0497-z · Cited by 16 · see citing works
Julian, A., Dugast, E., Ragot, S., Krolak‐Salmon, P., Berrut, G., DANTOINE, T. F., Hommet, C., Hanon, O., Page, G., & Paccalin, M. (2015) · Aging Clinical and Experimental Research · doi:10.1007/s40520-015-0332-5 · Cited by 15 · see citing works
Recent Trends in Active and Passive Immunotherapies of Alzheimer’s Disease
Alshamrani, M. (2023) · Antibodies · doi:10.3390/antib12020041 · Cited by 16 · see citing works
Zhang, G., Wang, J., Guo, Y., & Shi, B. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.7142 · Cited by 14 · see citing works
Gut–brain–bone marrow axis in hypertension
Li, J., Raizada, M. K., & Richards, E. M. (2020) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000678 · Cited by 13 · see citing works
Critical Role of Monocyte Recruitment in Optic Nerve Damage Induced by Experimental Optic Neuritis
Aranda, M. L., Guerrieri, D., Piñero, G., Fleitas, M. F. G., Altschuler, F., Diéguez, H. H., Sarmiento, M. I. K., Chianelli, M. S., Sande, P. H., Dorfman, D., et al. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-1608-0 · Cited by 13 · see citing works
MONOCYTIC CHEMOTACTIC PROTEIN-1 IN PHYSIOLOGY AND MEDICINE (REVIEW OF LITERATURE)
Kolotov, K. A., & Rasputin, P. (2018) · Perm Medical Journal · doi:10.17816/pmj35399-105 · Cited by 11 · see citing works
The Orphan C2orf40 Gene is a Neuroimmune Factor in Alzheimer's Disease.
Podvin, S., Miller, M. C., Rossi, R., Chukwueke, J., Donahue, J. E., Johanson, C. E., Baird, A., & Stopa, E. G. (2016) · PubMed · Cited by 11 · see citing works
Role of PUMA in the methamphetamine-induced migration of microglia
Zhao, L., Du, L., Zhang, Y., Chao, J., Duan, M., Yao, H., Shen, C., & Zhang, Y. (2018) · Metabolic Brain Disease · doi:10.1007/s11011-018-0319-y · Cited by 9 · see citing works
Association of CXCL 1 promoter polymorphism with ischaemic stroke in K orean population
Park, H. J., Yun, D. H., Kim, S. K., Chung, J. ‐., Lee, J. S., Park, H. ‐., Chon, J., Kim, D. H., Yoo, S. D., & Kim, H. ‐. (2012) · International Journal of Immunogenetics · doi:10.1111/iji.12009 · Cited by 9 · see citing works
Menasria, R., Canivet, C., Piret, J., Gosselin, J., & Boivin, G. (2016) · PLoS ONE · doi:10.1371/journal.pone.0168034 · Cited by 9 · see citing works
Neuropathological links between T2DM and LOAD: systematic review and meta-analysis
Lemche, E., Hortobágyi, T., Kiecker, C. M., & Turkheimer, F. (2025) · Physiological Reviews · doi:10.1152/physrev.00040.2024 · Cited by 8 · see citing works
Unveiling the theranostic potential of SPIONs in Alzheimer's disease management
Aminyavari, S., Afshari, A. R., Ahmadi, S. S., Kesharwani, P., Sanati, M., & Sahebkar, A. (2024) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2024.09.022 · Cited by 5 · see citing works
Celichowski, P., Jopek, K., Szyszka, M., Milecka, P., Tyczewska, M., Sakhanova, S., Szaflarski, W., Malendowicz, L. K., & Ruciński, M. (2021) · Advances in Clinical and Experimental Medicine · doi:10.17219/acem/136172 · Cited by 4 · see citing works
Infections with Chlamydia pneumoniae and SARS-CoV-2 and Alzheimer’s disease pathogenesis
Romanella, A., McCall, M., Corwin, R., Faruq, A. A., Lingo, E. G., Bhambhani, S., Hammond, C. J., & Balin, B. J. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1587782 · Cited by 4 · see citing works
Sheikh, M. A., Moon, M. P., Wright, C. B., Gutierrez, J., Liu, M., Rundek, T., Cheung, K., Hornig, M., & Elkind, M. S. V. (2024) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2024.100937 · Cited by 3 · see citing works
Inflammatory Mediators of Alzheimer’s Disease Characterized in a Mouse Model (APP/PS1)
Jorda, A., Alvarez-Gamez, K., Campo-Palacio, I., Campos-Campos, J., Colmena, C., Singh, S. K., Miralles, M. J. C., Aldasoro, C., Aldasoro, M., & Vallés, S. L. (2026) · NeuroSci · doi:10.3390/neurosci7010023 · Cited by 2 · see citing works
Merino, J. J., Rodriguez, J. J., Busquets, X., Álvarez-Vicente, I., Cabaña-Muñoz, M. E., Flores, A. I., & Tolédano, A. (2026) · Biomolecules · doi:10.3390/biom16060855 · Cited by 2 · see citing works
Wasiak, S., Fu, L., Daze, E., Gilham, D., Rakai, B. D., Stotz, S. C., Tsujikawa, L. M., Sarsons, C. D., Studer, D., Rinker, K. D., et al. (2023) · Translational Neuroscience · doi:10.1515/tnsci-2022-0332 · Cited by 2 · see citing works
Is Alzheimer's Associated Amyloid Beta an Innate Immune Protein
Kandel, R., White, M. R., Hseih, I.-N., & Hartshorn, K. L. (2016) · InTech eBooks · doi:10.5772/63021 · Cited by 1 · see citing works
Do Chemokines Have a Role in the Pathophysiology of Depression?
Singhal, G., & Baune, B. T. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811073-7.00008-8 · Cited by 2 · see citing works
- Authors
- Hickman, S. E., & Khoury, J. E.
- Affiliations
- Harvard University (US)
- ORCID
- Hickman, Suzanne E.
- Venue
- CNS & Neurological Disorders - Drug Targets
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2010-04-01
- Volume
- 9
- Issue
- 2
- Pages
- 168-173
- ISSN
- 1568-007X (ISSN-L)
- 1871-5273
- PMC
- PMC3684802
- OpenAlex
- W2060964242
- Cited by
- 120
- References
- 59
- Citations by year
- 2026: 8 · 2025: 4 · 2024: 8 · 2023: 4 · 2022: 1 · 2021: 5 · 2020: 9 · 2019: 6 · 2018: 8 · 2017: 11 · 2016: 11 · 2015: 8 · 2014: 12 · 2013: 9 · 2012: 7
- FWCI
- 4.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- CNS & Neurological Disorders - Drug Targets (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS059005, R01NS059005)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- Alzheimer's disease, mononuclear phagocytes, monocytes, microglia, chemokines, MCP-1, CCR2, amyloid-beta, amyloid plaques, neuroinflammation, blood-brain barrier, monocyte recruitment
- MeSH terms
- Alzheimer Disease, Animals, Chemotaxis, Leukocyte, Encephalitis, Humans, Leukocytes, Mononuclear, Phagocytes, Amyloid beta-Peptides, Chemokine CCL2, Myeloid Progenitor Cells, Mice, Receptors, CCR2, Plaque, Amyloid
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