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Migration of neutrophils targeting amyloid plaques in Alzheimer's disease mouse model
Open accessAbstract
Immune responses in the brain are thought to play a role in disorders of the central nervous system, but an understanding of the process underlying how immune cells get into the brain and their fate there remains unclear. In this study, we used a 2-photon microscopy to reveal that neutrophils infiltrate brain and migrate toward amyloid plaques in a mouse model of Alzheimer's disease. These findings suggest a new molecular process underlying the pathophysiology of Alzheimer's disease.
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“neutrophils have been shown to modulate Alzheimer’s disease pathology [52, 53].”
From IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia (2019) · cites this paper as [52]
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Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1202-06.2006 · Cited by 3,530 · cited 1×
“The neutrophils that precursor protein 695 and 2 mutations (M146L and L286V) of human presenilin-1 (Oakley et al., 2006).”
BackgroundNLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice
Heneka, M. T., Kummer, M. P., Stutz, A., Delekate, A., Schwartz, S., Vieira-Saecker, A., Griep, A., Axt, D., Remus, A., Tzeng, T.-C., et al. (2013) · Nature · doi:10.1038/nature11729 · Cited by 2,898
The NALP3 inflammasome is involved in the innate immune response to amyloid-β
Halle, A., Hornung, V., Petzold, G. C., Stewart, C. R., Monks, B. G., Reinheckel, T., Fitzgerald, K. A., Latz, E., Moore, K. J., & Golenbock, D. T. (2008) · Nature Immunology · doi:10.1038/ni.1636 · Cited by 2,441 · cited 1×
“However, controversial findings regarding the toxic properties of infiltrated immune cells in the central nervous system diseases have been reported (Halle et al., 2008; Heneka et al., 2013).”
BackgroundThe role of microglia in amyloid clearance from the AD brain
Lee, C. Y. D., & Landreth, G. E. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0433-4 · Cited by 701
Immune activation in brain aging and neurodegeneration: too much or too little?
Lucin, K. M., & Wyss-Coray, T. (2009) · Neuron · doi:10.1016/j.neuron.2009.08.039 · Cited by 679
Deciphering the mechanism underlying late-onset Alzheimer disease
Krstic, D., & Knuesel, I. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.236 · Cited by 457
Klunk, W. E., Bacskai, B. J., Mathis, C. A., Kajdasz, S. T., McLellan, M. E., Frosch, M. P., Debnath, M. L., Holt, D. P., Wang, Y., & Hyman, B. T. (2002) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/61.9.797 · Cited by 412
Neumann, J. H. L., Sauerzweig, S., Rönicke, R., Gunzer, F., Dinkel, K., Ullrich, O., Gunzer, M., & Reymann, K. G. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0060-08.2008 · Cited by 261 · cited 1×
“Moreover, a recent study has shown that microglia is effective in invading neutrophil granulocytes (Neumann et al., 2008).”
BackgroundA Craniotomy Surgery Procedure for Chronic Brain Imaging
Mostany, R., & Portera‐Cailliau, C. (2008) · Journal of Visualized Experiments · doi:10.3791/680 · Cited by 182
Tiffany, H. L., Lavigne, M. C., Cui, Y., Wang, J., Leto, T. L., Gao, J., & Murphy, P. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101031200 · Cited by 161 · cited 1×
“Although the underlying mechanisms for this observation are currently unclear, Ab itself might play a role in chemotaxis (Joslin et al., 1992; Tiffany et al., 2001).”
Background
Cited by
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Neutrophils promote Alzheimer's disease–like pathology and cognitive decline via LFA-1 integrin
Zenaro, E., Pietronigro, E., Bianca, V. D., Piacentino, G., Marongiu, L., Budui, S., Turano, E., Rossi, B., Angiari, S., Dusi, S., et al. (2015) · Nature Medicine · doi:10.1038/nm.3913 · Cited by 865
The blood-brain barrier in Alzheimer’s disease
Zenaro, E., Piacentino, G., & Constantin, G. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.07.007 · Cited by 767
“Accordingly, other recent imaging studies have shown that Gr1 + cells extravasate through the BBB in the brain parenchyma of 5xFAD mice and migrate towards A β plaques, suggesting a role for A β in neutrophil recruitment during AD (Baik et al., 2014).”
Neutrophils as emerging therapeutic targets
Németh, T., Sperandio, M., & Mócsai, A. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0054-z · Cited by 676
Neutrophils as protagonists and targets in chronic inflammation
Soehnlein, O., Steffens, S., Hidalgo, A., & Weber, C. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.10 · Cited by 623
Neuroinflammation in Alzheimer disease
Heneka, M. T., van der Flier, W. M., Jessen, F., Hoozemanns, J., Thal, D. R., Boche, D., Brosseron, F., Teunissen, C., Zetterberg, H., Jacobs, A. H., et al. (2025) · Nature Reviews Immunology · doi:10.1038/s41577-024-01104-7 · Cited by 638
“Neutrophils adhere in brain vessels and migrate into the parenchyma but they also obstruct blood flow by plugging brain capillaries 371–373 .”
Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight
Shi, Y., & Holtzman, D. M. (2018) · Nature Reviews Immunology · doi:10.1038/s41577-018-0051-1 · Cited by 595
Neutrophils in Homeostasis, Immunity, and Cancer
Nicolás-Ávila, J. Á., Adrover, J. M., & Hidalgo, A. (2017) · Immunity · doi:10.1016/j.immuni.2016.12.012 · Cited by 413
“Brains from transgenic mice that reproduce the cardinal features of Alzheimer’s disease are infiltrated by neutrophils (Baik et al., 2014), a process that requires specific activation of the integrin LFA-1 by amyloid b peptides.”
BackgroundMicroglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau
Kang, S. S., Ebbert, M. T. W., Baker, K. E., Cook, C., Wang, X., Sens, J. P., Kocher, J.-P., Petrucelli, L., & Fryer, J. D. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20180653 · Cited by 260
“Interestingly, CNS neutrophil recruitment/extravasation has been shown to exacerbate pathology and cognitive impairment in AD models (Baik et al., 2014; Zenaro et al., 2015).”
BackgroundEmerging roles of innate and adaptive immunity in Alzheimer’s disease
Chen, X., & Holtzman, D. M. (2022) · Immunity · doi:10.1016/j.immuni.2022.10.016 · Cited by 297
The neuroimmune axis of Alzheimer’s disease
Jorfi, M., Maaser‐Hecker, A., & Tanzi, R. E. (2023) · Genome Medicine · doi:10.1186/s13073-023-01155-w · Cited by 313
“Infiltrating neutrophils found in the brains of AD patients and transgenic animal models (Table 2) [207, 260] have attracted growing interest in the last few years in MS and AD [261].”
BackgroundIn vitro Models of Neurodegenerative Diseases
Slanzi, A., Iannoto, G., Rossi, B., Zenaro, E., & Constantin, G. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00328 · Cited by 315
Blood cells and endothelial barrier function
Rodrigues, S. F., & Granger, D. N. (2015) · Tissue Barriers · doi:10.4161/21688370.2014.978720 · Cited by 295
“Neutrophils Neutrophils have been implicated as mediators of the increased vascular permeability that accompanies a variety of pathological conditions, including ischemia-reperfusion,(71) sepsis,(72) cancer(73,74) and neurological diseases.(75) A role for neutrophils in these conditions is largely based on 2 observati…”
BackgroundBaik, S. H., Kang, S., Son, S. M., & Mook-Jung, I. (2016) · Glia · doi:10.1002/glia.23074 · Cited by 234
“Open skull craniotomy surgery was performed for long-term in vivo imaging, as described previously, with minor modifications (Baik et al., 2014).”
MethodSelf-citation(ADNI), A. D. N. I., Deming, Y., The Alzheimer Disease Genetic Consortium (ADGC), Li, Z., Kapoor, M., Harari, O., Del-Aguila, J. L., Black, K., Carrell, D., Cai, Y., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1685-y · Cited by 231
Neutrophil swarming: an essential process of the neutrophil tissue response
Kienle, K., & Lämmermann, T. (2016) · Immunological Reviews · doi:10.1111/imr.12458 · Cited by 229
High-Throughput Screening Platforms in the Discovery of Novel Drugs for Neurodegenerative Diseases
Aldewachi, H. S., Al-Zidan, R. N., Conner, M. T., & Salman, M. M. (2021) · Bioengineering · doi:10.3390/bioengineering8020030 · Cited by 217
Kim, D., Moon, H., Baik, S. H., Singha, S., Jun, Y. W., Wang, T., Kim, K. H., Park, B. S., Jung, J., Mook‐Jung, I., et al. (2015) · Journal of the American Chemical Society · doi:10.1021/jacs.5b03548 · Cited by 205
Self-citationPeripheral inflammatory biomarkers in Alzheimer’s disease: a brief review
Park, J., Han, S.-H., & Mook‐Jung, I. (2020) · BMB Reports · doi:10.5483/bmbrep.2020.53.1.309 · Cited by 206
“migration of neutrophils traversing the BBB into the brain targeting amyloid plaques (10), recruitment of monocytes/ macrophages via CCL2 or CX3CL1 to the sites of inflammatory”
BackgroundSelf-citationYin, T., Yang, L., Liu, Y., Zhou, X., Sun, J., & Liu, J. (2015) · Acta Biomaterialia · doi:10.1016/j.actbio.2015.06.035 · Cited by 198
Neutrophils in traumatic brain injury (TBI): friend or foe?
Liu, Y., Li, S., & Dai, S.-S. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1173-x · Cited by 197
“Neutrophils could also drive initiation of the AD-like symptoms [157] and participate in the formation of Aβ plaques [158].”
Munir, H., Jones, J. O., Janowitz, T., Hoffmann, M. H., Euler, M., Martins, C. P., Welsh, S. J., & Shields, J. D. (2021) · Nature Communications · doi:10.1038/s41467-021-20982-2 · Cited by 186
NETosis in Alzheimer’s Disease
Pietronigro, E. C., Bianca, V. D., Zenaro, E., & Constantin, G. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00211 · Cited by 179
“org March 2017 | Volume 8 | Article 211 memory deficit (8, 32).”
BackgroundResultInfluentialNeutrophil contribution to spinal cord injury and repair
Neirinckx, V., Coste, C., Franzen, R., Gothot, A., Rogister, B., & Wislet‐Gendebien, S. (2014) · Journal of Neuroinflammation · doi:10.1186/s12974-014-0150-2 · Cited by 171
“New insights in the physiopathological processes of AD showed that neutrophils migrate towards amyloid plaques, maybe suggesting a potential interaction worthy of thorough characterization [55] in order to specify the role of neutrophils in AD pathogenesis.”
BackgroundSingle-Cell RNA Sequencing of Peripheral Blood Reveals Immune Cell Signatures in Alzheimer’s Disease
Xu, H., & Jia, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.645666 · Cited by 149
Neutrophils in aging and aging‐related pathologies
Avondt, K. V., Strecker, J., Tulotta, C., Minnerup, J., Schulz, C., & Soehnlein, O. (2022) · Immunological Reviews · doi:10.1111/imr.13153 · Cited by 155
Mast cells and neutrophils mediate peripheral motor pathway degeneration in ALS
Trías, E., King, P. H., Si, Y., Kwon, Y., Varela, V., Ibarburu, S., Kovacs, M., Moura, I. C., Beckman, J. S., Hermine, O., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.123249 · Cited by 145
The Emerging Role of Central and Peripheral Immune Systems in Neurodegenerative Diseases
Zang, X., Chen, S., Zhu, J., Ma, J., & Zhai, Y. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.872134 · Cited by 139
“In addition, the results of animal studies of AD suggest that neutrophils may be associated with the destruction of the BBB (Baik et al., 2014).”
BackgroundDopaminergic Regulation of Innate Immunity: a Review
Pinoli, M., Marino, F., & Cosentino, M. (2017) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-017-9749-2 · Cited by 131
Smyth, L. C. D., Murray, H. C., Hill, M. J., van Leeuwen, E., Highet, B., Magon, N. J., Osanlouy, M., Mathiesen, S. N., Mockett, B. G., Singh‐Bains, M. K., et al. (2022) · Acta Neuropathologica Communications · doi:10.1186/s40478-022-01347-2 · Cited by 133
Felice, F. G. D., & Lourenco, M. V. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00094 · Cited by 122
“Consistently, evidence for gliosis and central infiltration of peripheral immune cells is often found in histopathological studies in AD mouse models (Yamanaka et al., 2012; Lourenco and Ledo, 2013; Yang et al., 2013; Baik et al., 2014; Ferreira et al., 2014; Monson et al., 2014).”
BackgroundNeuroinflammation in Alzheimer’s disease: insights from peripheral immune cells
Zhang, Q., Yang, G., Luo, Y., Jiang, L., Chi, H., & Tian, G. (2024) · Immunity & Ageing · doi:10.1186/s12979-024-00445-0 · Cited by 138
“Concurrently, a different study employing two-photon microscopy on a mouse AD model observed neutrophil infiltration in the brain parenchyma, with a propensity to migrate towards Aβ plaques [41].”
BackgroundNeuropathogenesis-on-chips for neurodegenerative diseases
Amartumur, S., Nguyen, H. M., Huynh, T., Kim, T. S., Woo, R., Oh, E., Kim, K. K., Lee, L. P., & Heo, C. (2024) · Nature Communications · doi:10.1038/s41467-024-46554-8 · Cited by 131
Self-citationProbiotics ameliorate intestinal pathophysiology in a mouse model of Alzheimer’s disease
Kaur, H., Nagamoto‐Combs, K., Golovko, S. A., Golovko, M. Y., Klug, M. G., & Combs, C. K. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.04.009 · Cited by 115
“…are several mechanisms proposed by which probiotic can modulate brain functions including vagal signaling (Bravo et al., 2011), neuronal pathways (Baik et al., 2014), microbial metabolites such as short chain fatty acid including acetate, butyrate, and lactate (Macfabe, 2012; Macfarlane and…”
BackgroundLRRK2 G2019S mutation attenuates microglial motility by inhibiting focal adhesion kinase
Choi, I., Kim, B., Byun, J.-W., Baik, S. H., Huh, Y. H., Kim, J.-H., Mook-Jung, I., Song, W. K., Shin, J.-H., Seo, H., et al. (2015) · Nature Communications · doi:10.1038/ncomms9255 · Cited by 112
Self-citationThe role of neutrophil granule proteins in neuroinflammation and Alzheimer’s disease
Stock, A. J., Kasus‐Jacobi, A., & Pereira, H. A. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1284-4 · Cited by 117
Systemic and CNS Inflammation Crosstalk: Implications for Alzheimer’s Disease
Paouri, E., & Georgopoulos, S. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666190321154618 · Cited by 109
Lämmermann, T. (2015) · Journal of Leukocyte Biology · doi:10.1189/jlb.1mr0915-403 · Cited by 112
“In several models of inflammation [12, 13], infection”
BackgroundKim, D. K., Park, J., Han, D., Yang, J., Kim, A., Woo, J., Kim, Y., & Mook-Jung, I. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0234-4 · Cited by 95
“In the brain parenchyma, the neutrophils adhere to amyloid plaques and phagocyte them [62].”
BackgroundSayed, A., Bahbah, E. I., Kamel, S., Barreto, G. E., Ashraf, G. M., & Elfil, M. (2020) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2020.577398 · Cited by 88
Kim, Y. R., Kim, Y. M., Lee, J., Park, J., Lee, J. E., & Hyun, Y. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.613733 · Cited by 85
Self-citationMigration 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
“Using 2photon microscopy the authors observed dynamic extravasation of these cells from blood vessels into the brain parenchyma of 9- to 13-month-old 5XFAD mice (Baik et al., 2014).”
Chun, H., Marriott, I., Lee, C. J., & Cho, H. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00797 · Cited by 77
“Among these immune cells, neutrophils are of great interest because they are key effector cells in many inflammatory responses, and they show a remarkable ability to migrate within and through blood vessels (84, 85).”
BackgroundSelf-citationCommon Peripheral Immunity Mechanisms in Multiple Sclerosis and Alzheimer's Disease
Rossi, B., Santos-Lima, B., Terrabuio, E., Zenaro, E., & Constantin, G. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.639369 · Cited by 84
“In AD brains, infiltrating neutrophils are closely associated with amyloid β deposits, and amyloid β peptides trigger the rapid integrin-dependent adhesion of neutrophils via G protein coupled receptors (10, 78).”
BackgroundGlymphatic System Pathology and Neuroinflammation as Two Risk Factors of Neurodegeneration
Szlufik, S., Kopeć, K., Szleszkowski, S., & Koziorowski, D. (2024) · Cells · doi:10.3390/cells13030286 · Cited by 84
“In a mouse model of AD, it has been observed that A β plaques act on neutrophils chemotactically by stimulating their migration across the BBB [85].”
BackgroundMicroRNA deregulation and chemotaxis and phagocytosis impairment in Alzheimer's disease
Guedes, J. R., Santana, I. J., Cunha, C., Duro, D., Almeida, M. R., Cardoso, A. M., de Lima, M. C. P., & Cardoso, A. L. (2015) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2015.11.004 · Cited by 77
“Although previous in vitro studies have suggested that Ab soluble monomers do not act as a direct chemoattractant for immune cells [29], it is believed that monocytes can potentially bind to vascular Ab deposits in brain vessels [2].”
BackgroundRivera-Escalera, F., Pinney, J. J., Owlett, L., Ahmed, H., Thakar, J., Olschowka, J. A., Elliott, M. R., & O’Banion, M. K. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1645-7 · Cited by 75
Volkman, R., Ben‐Zur, T., Kahana, A., Garty, B. Z., & Offen, D. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00990 · Cited by 72
“In the 5XFAD mouse model of AD, enhanced neutrophils extravasate into the central nervous system (CNS) and migrate toward amyloid plaques (Baik et al., 2014; Zenaro et al., 2015).”
BackgroundInitiative, A. D. N., Bawa, K. K., Krance, S. H., Herrmann, N., Cogo‐Moreira, H., Ouk, M., Yu, D., Wu, C., Black, S. E., Lanctôt, K. L., et al. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01750-3 · Cited by 72
Association of Peripheral Blood Cell Profile With Alzheimer's Disease: A Meta-Analysis
Huang, L., Zhang, C., Wang, Y., & Wang, J. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.888946 · Cited by 76
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Rawat, K., Syeda, S., & Shrivastava, A. (2021) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09951-1 · Cited by 75
Núñez, C., Stephan‐Otto, C., Usall, J., Bioque, M., Lobo, A., González-Pinto, A. M., Pina‐Camacho, L., Vieta, E., Castro‐Fornieles, J., Rodríguez–Jiménez, R., et al. (2018) · Schizophrenia Bulletin · doi:10.1093/schbul/sby113 · Cited by 68
Neutrophil extracellular traps in central nervous system pathologies: A mini review
Shafqat, A., Eddin, A. N., Adi, G., Al-Rimawi, M., Rab, S. A., Abu-Shaar, M., Adi, K., AlKattan, K. M., & Yaqinuddin, A. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1083242 · Cited by 62
“Intraparenchymal neutrophils specifically migrated toward areas of Aβ plaques (120).”
BackgroundEarly-Onset Alzheimer Disease and Candidate Risk Genes Involved in Endolysosomal Transport
Kunkle, B. W., Vardarajan, B. N., Naj, A. C., Whitehead, P. L., Rolati, S., Slifer, S., Carney, R. M., Cuccaro, M. L., Vance, J. M., Gilbert, J. R., et al. (2017) · JAMA Neurology · doi:10.1001/jamaneurol.2017.1518 · Cited by 58
Dietary Regulation of Gut-Brain Axis in Alzheimer’s Disease: Importance of Microbiota Metabolites
Frausto, D. M., Forsyth, C. B., Keshavarzian, A., & Voigt, R. M. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.736814 · Cited by 61
“, T cells) immune cells can infiltrate the CNS and accumulate near areas of Aβ and tau pathology (Fiala et al., 2002; Baik et al., 2014; Merlini et al., 2018; Gate et al., 2020).”
BackgroundNeutrophils as a potential therapeutic target in Alzheimer’s disease
Aries, M. L., & Hensley‐McBain, T. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1123149 · Cited by 62
“(9) 5xFAD TG6799; B6SJL-Tg [APPSwF1Lon, PSEN*M146L* L286V]6799Vas/J stock no.”
BackgroundDeep insight into neutrophil trafficking in various organs
Hyun, Y., & Hong, C.-W. (2017) · Journal of Leukocyte Biology · doi:10.1189/jlb.1ru1216-521r · Cited by 63
Self-citationThe emerging role of neutrophils in neurodegeneration
Rossi, B., Constantin, G., & Zenaro, E. (2019) · Immunobiology · doi:10.1016/j.imbio.2019.10.014 · Cited by 60
Zou, C., Mifflin, L., Hu, Z., Zhang, T., Shan, B., Wang, H., Xing, X., Zhu, H., Adiconis, X., Levin, J. Z., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108447 · Cited by 61
Genetic Approaches Using Zebrafish to Study the Microbiota–Gut–Brain Axis in Neurological Disorders
Lee, J. G., Cho, H.-J., Jeong, Y.-M., & Lee, J.-S. (2021) · Cells · doi:10.3390/cells10030566 · Cited by 57
Self-citationAssociation of peripheral immunity with cognition, neuroimaging, and Alzheimer’s pathology
Hou, J., Ou, Y., Xu, W., Zhang, P., Tan, L., Yu, J., & Initiative, O. B. O. A. D. N. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-00968-y · Cited by 57
“Previous articles have investigated the association of peripheral immunity with AD, but they were limited to basic research [5, 6], animal research [18, 19, 30], review [26, 40, 42], and rough cross-sectional analyses [7], and most studies were of small samples [28, 33, 36, 44, 51, 56, 57].”
BackgroundBang, S., Lee, S., Choi, N., & Kim, H. N. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202002119 · Cited by 57
Ramos-Cejudo, J., Johnson, A. D., Beiser, A., Seshadri, S., Salinas, J., Berger, J. S., Fillmore, N. R., Do, N., Zheng, C., Kovbasyuk, Z., et al. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.773984 · Cited by 49
Imaging of Leukocyte Trafficking in Alzheimer’s Disease
Pietronigro, E. C., Zenaro, E., & Constantin, G. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00033 · Cited by 52
“However, recent TPLSM studies have shown that circulating leukocytes migrate into the brain parenchyma of AD mice, revealing previously unknown mechanisms of AD pathogenesis and helping to identify new therapeutic strategies for AD (19, 20).”
BackgroundA quadrupolar two-photon fluorescent probe for in vivo imaging of amyloid-β plaques
Heo, C. H., Sarkar, A. R., Baik, S. H., Jung, T. S., Kim, J. J., Kang, H., Mook‐Jung, I., & Kim, H. M. (2016) · Chemical Science · doi:10.1039/c6sc00355a · Cited by 53
Self-citationShi, J., Peng, H. Y., You, S., Liu, Y., Xu, J., Xu, Y., Liu, H., Shi, R., Cao, Y., & Liu, C. (2018) · European Journal of Neurology · doi:10.1111/ene.13575 · Cited by 53
“Recent studies demonstrated that neutrophils can enter brain tissues that other white blood cells cannot penetrate [30,31].”
BackgroundWu, C., Bawa, K. K., Ouk, M., Leung, N., Yu, D., Lanctôt, K. L., Herrmann, N., Pakosh, M. T., & Swardfager, W. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101130 · Cited by 53
Guo, Y., Zeng, H., & Chen, G. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/9931742 · Cited by 53
“Studies have shown that neutrophil depletion can improve the cognitive function and reduce AD-associated pathological damage in AD model mice [56, 57].”
BackgroundNeutrophils as emerging protagonists and targets in chronic inflammatory diseases
Rawat, K., & Shrivastava, A. (2022) · Inflammation Research · doi:10.1007/s00011-022-01627-6 · Cited by 55
“Various clinical and animal studies have shown that neutrophils may translocate to the cerebral blood vessels and co-localize with amyloid plaques within the brain parenchyma [56].”
BackgroundShi, M., Chu, F., Zhu, F., & Zhu, J. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-023-03003-5 · Cited by 52
“More than a decade ago, Baik, et al. have observed the peripheral neutrophils infiltrating into the brains of both AD patients and its Tg models (5xFAD and 3xTg-AD mice), and existing in the areas with Aβ deposits [71, 72].”
BackgroundUltrathin Dual‐Scale Nano‐ and Microporous Membranes for Vascular Transmigration Models
Salminen, A. T., Zhang, J., Madejski, G. R., Khire, T. S., Waugh, R. E., McGrath, J. L., & Gaborski, T. R. (2019) · Small · doi:10.1002/smll.201804111 · Cited by 50
Wyatt-Johnson, S. K., & Brutkiewicz, R. R. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.592359 · Cited by 50
“, 2020), neutrophils (Baik et al., 2014; Zenaro et al., 2015; Vida et al., 2017; Park et al., 2019), NK cells (Marsh et al.”
BackgroundPark, J., Baik, S. H., Mook‐Jung, I., Irimia, D., & Cho, H. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02231 · Cited by 46
“Among them, neutrophils are the body’s most abundant and frontline immune cells, respond with both central and peripheral immune effectors during the progression of AD (17).”
BackgroundSelf-citationKretzschmar, G. C., Bumiller‐Bini, V., Filho, M. A. G., Zonta, Y. R., Yu, K. S. T., de Souza, R. L. R., Dias‐Melicio, L. A., & Boldt, A. B. W. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.630869 · Cited by 42
Page, A. Y. L., Lamoureux, J., Bourgade, K., Frost, E. H., Pawelec, G., Witkowski, J. M., Larbi, A., Dupuis, G., & Fülöp, T. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170124 · Cited by 42
Cellular transcriptional alterations of peripheral blood in Alzheimer’s disease
Song, L., Yang, Y., Guo, Q., & Zhao, X. (2022) · BMC Medicine · doi:10.1186/s12916-022-02472-4 · Cited by 40
“Consistent with the extravasation migration of neutrophils into brain [31, 36], we observed that the absolute abundance of neutrophils was significantly increased in AD brains in both cerebellum (CBE) (P = 4.”
BackgroundXia, X., He, X., Zhao, T., Yang, J., Bi, Z., Fu, Q., Liu, J., Ao, D., Wei, Y., & Wei, X. (2023) · Cell Proliferation · doi:10.1111/cpr.13529 · Cited by 38
Neutrophils in animal models of autoimmune disease
Németh, T., Mócsai, A., & Lowell, C. A. (2016) · Seminars in Immunology · doi:10.1016/j.smim.2016.04.001 · Cited by 39
The Role of Sphingolipids and Specialized Pro-Resolving Mediators in Alzheimer’s Disease
de Wit, N. M., Mol, K., Rodríguez‐Lorenzo, S., de Vries, H. E., & Kooij, G. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.620348 · Cited by 40
Barkaway, A., Attwell, D., & Korte, N. (2022) · Neurophotonics · doi:10.1117/1.nph.9.3.031914 · Cited by 38
“Nils Korte studied physiology in Glasgow and Melbourne, and did his PhD at University College London on the regulation of CBF in health, stroke, and AD.”
BackgroundInfluentialMain, E. N., Cruz, T. M., & Bowlin, G. L. (2023) · Regenerative Biomaterials · doi:10.1093/rb/rbad070 · Cited by 34
Inflammatory pathway analytes predicting rapid cognitive decline in MCI stage of Alzheimer’s disease
Pillai, J. A., Bena, J., Bebek, G., Bekris, L. M., Bonner‐Jackson, A., Kou, L., Pai, A., Sørensen, L., Neilsen, M., Rao, S. M., et al. (2020) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51109 · Cited by 34
Changes in the structure and function of the brain years after Pre-eclampsia
Ijomone, O. K., Shallie, P. D., & Naicker, T. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.06.006 · Cited by 31
Unzeta, M., Hernández‐Guillamón, M., Sun, P., & Solé, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073365 · Cited by 34
PET Imaging of Neutrophils Infiltration in Alzheimer's Disease Transgenic Mice
Kong, Y., Liu, K., Hua, T., Zhang, C., Sun, B., & Guan, Y. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.523798 · Cited by 31
“In the transgenic AD model mice brain, there is also substantial neutrophil infiltration to Aβ plaques, and neutrophil depletion or trafficking inhibition can reduce the AD-like neuropathology and improve the cognitive dysfunction (10, 11).”
BackgroundThe role of integrins in brain health and neurodegenerative diseases
Cui, Y., Rõlova, T., & Fagerholm, S. C. (2024) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2024.151441 · Cited by 32
Alzheimer’s disease: The role of T lymphocytes in neuroinflammation and neurodegeneration
Asamu, M. O., Oladipo, O. O., Abayomi, O. A., & Adebayo, A. A. (2023) · Brain Research · doi:10.1016/j.brainres.2023.148589 · Cited by 32
A Brief Overview of Neutrophils in Neurological Diseases
Chakraborty, S., Tabrizi, Z., Bhatt, N. N., Franciosa, S. A., & Bracko, O. (2023) · Biomolecules · doi:10.3390/biom13050743 · Cited by 29
Myeloid cells in vascular dementia and Alzheimer's disease: Possible therapeutic targets?
García‐Culebras, A., Cuartero, M. I., Peña‐Martínez, C., Moraga, A., Vázquez‐Reyes, S., Castro-Millán, F. J., Cortés‐Canteli, M., Lizasoaín, I., & Moro, M. Á. (2023) · British Journal of Pharmacology · doi:10.1111/bph.16159 · Cited by 27
“In this sense, different studies in AD patients have clearly demonstrated that neutrophils infiltrate into the brain parenchyma (Baik et al., 2014; Zenaro et al., 2015).”
BackgroundResultXia, H., Feng, Y., Zhu, H., Yang, D., Wang, C., Wang, Z., Zhang, H., Pan, W., Zhao, Y., Initiative, A. D. N., et al. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03432-1 · Cited by 30
“Further longitudinal human trials and animal studies are warranted to validate our fi ndings and elucidate the underlying molecular mechanisms.”
Immune dysfunction in Alzheimer disease
Butovsky, O., Rosenzweig, N., Kleemann, K. L., Jorfi, M., Kuchroo, V. K., Tanzi, R. E., & Weiner, H. L. (2025) · Nature reviews. Neuroscience · doi:10.1038/s41583-025-00997-0 · Cited by 41
“Neutrophils are another myeloid cell type that interacts with the brain borders and have been shown to infiltrate the brains of people with AD 50,129 and AD mouse models 130,131 .”
Panayiotou, E., Fella, E., Andreou, S., Papacharalambous, R., Gerasimou, P., Costeas, P., Angeli, S., Kousiappa, I., Papacostas, S., & Kyriakides, T. (2019) · PLoS ONE · doi:10.1371/journal.pone.0225417 · Cited by 26
“A neutrophil/monocyte marker (Ly6C/G) has been found on cells migrating towards Aβ plaques in an AD mouse model [26].”
BackgroundIs Targeting the Inflammasome a Way Forward for Neuroscience Drug Discovery?
Swanton, T., Cook, J., Beswick, J. A., Freeman, S., Lawrence, C. B., & Brough, D. (2018) · SLAS DISCOVERY · doi:10.1177/2472555218786210 · Cited by 26
Interleukin 22 and its association with neurodegenerative disease activity
Chen, W., Wang, J., Yang, H., Sun, Y., Chen, B., Liu, Y., Han, Y., Shan, M., & Zhan, J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.958022 · Cited by 27
Qi, F., Zuo, Z., Hu, K., Wang, R., Wu, T., Liu, H., Tang, J., Wang, Q., Xie, Y., Tan, L., et al. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02097-w · Cited by 24
“Neutrophils are the key effector cells of early innate immunity and contribute to in fl ammation in the brain [10, 56] and periphery [6].”
BackgroundJacobs, T., Jacobson, S. R., Fortea, J., Berger, J. S., Vedvyas, A., Marsh, K., He, T., Gutiérrez‐Jiménez, E., Fillmore, N. R., Gonzalez, M., et al. (2024) · Immunity & Ageing · doi:10.1186/s12979-024-00435-2 · Cited by 27
“This was done for both cohorts: the ADNI ( A ) and NYU ( B ) considered an immune-privileged site, neutrophils and NETs have been shown to aggregate in the cerebral small vessels of AD patients, particularly near Aβ plaques and tau tangles [7, 8, 56].”
BackgroundMethodKatayama, H. (2019) · Brain and Behavior · doi:10.1002/brb3.1504 · Cited by 24
“Studies using 2-photon microscopy revealed substantial neutrophil migration toward Aβ plaques in transgenic AD mice brain model (Baik et al., 2014; Zenaro et al., 2015).”
BackgroundCD8+ T cells exacerbate AD-like symptoms in mouse model of amyloidosis
Wang, X., Campbell, B., Bodogai, M., McDevitt, R. A., Patrikeev, A., Gusev, F. E., Ragonnaud, E., Kumaraswami, K., Shirenova, S. D., Vardy, K., et al. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.08.045 · Cited by 30
Neutrophils: a subgroup of neglected immune cells in ALS
Cao, W., & Fan, D. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1246768 · Cited by 23
“showed dynamic imaging of neutrophils entering into brain parenchyma in AD mice, but no such migration was found in wild-type mice (46).”
BackgroundNetzahualcoyotzi, C., Santillán‐Cigales, J. J., Adalid-Peralta, L. V., & Velasco, I. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16106 · Cited by 24
“Of note is the fact that neutrophils migrate toward A β plaques, suggesting a direct role of this peptide in neutrophil recruitment during AD (Baik et al., 2014 ; Zenaro et al., 2015).”
IL-22, a vital cytokine in autoimmune diseases
Li, J., Wu, Z., Wu, Y., Hu, X., Yang, J., Zhu, D., Wu, M., Li, X., Bentum‐Ennin, L., & Hu, W. (2024) · Clinical & Experimental Immunology · doi:10.1093/cei/uxae035 · Cited by 23
Metadata
- Authors
- Baik, S. H., Cha, M.-Y., Hyun, Y.-M., Cho, H., Hamza, B., Kim, D. K., Han, S.-H., Choi, H., Kim, K. H., Moon, M., Lee, J., Kim, M., Irimia, D., & Mook-Jung, I.
- Affiliations
- Seoul National University (KR)
- University of Rochester Medicine (US)
- Harvard University (US)
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 35
- Issue
- 6
- Pages
- 1286-1292
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC4248665
- OpenAlex
- W2023641365
- Cited by
- 181
- References
- 19
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 26 · 2023: 17 · 2022: 22 · 2021: 16 · 2020: 16 · 2019: 10 · 2018: 13 · 2017: 13 · 2016: 9 · 2015: 11 · 2014: 3
- FWCI
- 6.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Research Foundation of Korea (2012R1A2A1A01002881)
- MRC (2011–0030738)
- Korea National Institute of Health ROAD R&D Program Project (A092058)
- Korea Institute of Science and Technology Institutional Program (2E24242-13–135)
- Cooperative Research Program for Agriculture Science & Technology Development (PJ009103)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- neutrophils, amyloid plaques, Alzheimer's disease, neutrophil migration, brain immune response, neuroinflammation, two-photon microscopy, mouse model
- MeSH terms
- Alzheimer Disease, Animals, Brain, Cell Movement, Cells, Cultured, Disease Models, Animal, Humans, Mice, Transgenic, Microscopy, Neutrophils, Mice, Molecular Imaging, Plaque, Amyloid
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