The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
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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Cites
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
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“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).”
BackgroundPhagocytosis of Amyloid-β and Inflammation: Two Faces of Innate Immunity in Alzheimer's Disease
Fiala, M., Cribbs, D. H., Rosenthal, M. J., & Bernard, G. W. (2007) · Journal of Alzheimer s Disease · doi:10.3233/jad-2007-11406 · Cited by 124 · cited 1×
“…disease (AD), beta-amyloid (Ab), has been shown to be associated with brain inflammatory responses and to activate microglia and monocytes (Fiala et al., 2007; Hickman and El Khoury, 2013; Krstic and Knuesel, 2013), raising the possibility that immune responses might play a role in the…”
BackgroundMacrophages in Alzheimer’s disease: the blood-borne identity
Gate, D., Rezai-Zadeh, K., Jodry, D., Rentsendorj, A., & Town, T. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0422-7 · Cited by 107
Aging and Neutrophils: There Is Still Much To Do
Fortin, C. F., McDonald, P. P., Lesur, O., & Fülöp, T. (2008) · Rejuvenation Research · doi:10.1089/rej.2008.0750 · Cited by 97
Joslin, G., Griffin, G. L., August, A. M., Adams, S. P., Fallon, R. J., Senior, R. M., & Perlmutter, D. H. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115934 · Cited by 68 · 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).”
BackgroundHow to Get from Here to There: Macrophage Recruitment in Alzheimers Disease
Rezai-Zadeh, K. P., Gate, D., Gowing, G., & Town, T. (2011) · Current Alzheimer Research · doi:10.2174/156720511795256017 · Cited by 64
The Innate Immune Response in the Central Nervous System and Its Role in Glioma Immune Surveillance
Friese, M. A., Steinle, A., & Weller, M. (2004) · Oncology Research and Treatment · doi:10.1159/000080371 · Cited by 32
On-demand, competing gradient arrays for neutrophil chemotaxis
Cho, H., Hamza, B. M., Wong, E. A., & Irimia, D. (2013) · Lab on a Chip · doi:10.1039/c3lc50959a · Cited by 30 · cited 6×
“4 kDa) along the channels were estimated to provide the original gradients more than 80% for an hour (Cho et al., 2013) and neutrophil migration was monitored for 2 hours.”
MethodInfluentialSelf-citationThe NeuroImmune System in Alzheimer's Disease: The Glass is Half Full
Hickman, S. E., & El Khoury, J. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2012-129027 · Cited by 29
Snyder, D. B., & Tilly, C. (1973) · American Sociological Review · doi:10.2307/2094222 · Cited by 4
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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 .”
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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