The DOI matches its Crossref record; 63 of the 64 references it cites were found in a registry or an index.
Depletion of NK Cells Improves Cognitive Function in the Alzheimer Disease Mouse Model
Open accessAbstract
Despite mounting evidence suggesting the involvement of the immune system in regulating brain function, the specific role of immune and inflammatory cells in neurodegenerative diseases remain poorly understood. In this study, we report that depletion of NK cells, a type of innate lymphocytes, alleviates neuroinflammation, stimulates neurogenesis, and improves cognitive function in a triple-transgenic Alzheimer disease (AD) mouse model. NK cells in the brains of triple-transgenic AD mouse model (3xTg-AD) mice exhibited an enhanced proinflammatory profile. Depletion of NK cells by anti-NK1.1 Abs drastically improved cognitive function of 3xTg-AD mice. NK cell depletion did not affect amyloid β concentrations but enhanced neurogenesis and reduced neuroinflammation. Notably, in 3xTg-AD mice depleted of NK cells, microglia demonstrated a homeostatic-like morphology, decreased proliferative response and reduced expression of neurodestructive proinflammatory cytokines. Together, our results suggest a proinflammatory role for NK cells in 3xTg-AD mice and indicate that targeting NK cells might unlock novel strategies to combat AD.
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“Such discrepancies may stem from differences in experimental models, including differences in NK cell deficiency which could contribute to the divergent outcomes observed [111].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [111]
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Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · cited 1×
“Gene pathway analysis was performed with the Database for Annotation, Visualization and Integrated Discovery (30, 31).”
MethodHuang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkn923 · Cited by 14,108 · cited 2×
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MethodMorris 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 · cited 1×
“We used a Morris Water Maze test (47) to examine the cognitive function of 3xTg-AD mice that were treated with anti-NK1.”
MethodTriple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126
Microglia in Alzheimer’s disease
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Neuroinflammation in Alzheimer's disease: current evidence and future directions
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“Adult neurogenesis was diminished in the inflamed brains of AD patients and transgenic AD mouse models, which might contribute to declined cognitive function in AD (48, 62).”
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TREM2 Maintains Microglial Metabolic Fitness in Alzheimer’s Disease
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“These microglia also exhibited intact expression of Trem2, a surface receptor that plays an essential role in promoting microglial metabolic fitness (63).”
BackgroundRole of Pro-Inflammatory Cytokines Released from Microglia in Neurodegenerative Diseases
Smith, J. A., Das, A., Ray, S. K., & Banik, N. L. (2012) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2011.10.004 · Cited by 1,165
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Items 101–113 of 113
Iba, M., Kwon, S., Kim, C., Szabo, M. P., Horan-Portelance, L., Lopez-Ocasio, M. D., Dagur, P. K., Overk, C., Rissman, R. A., & Masliah, E. (2024) · Figshare · doi:10.6084/m9.figshare.25608801
Fung, I. T. H., Zhang, Y., Shin, D. S., Sankar, P., Sun, X., D’Souza, S. S., Song, R., Kuentzel, M. L., Chittur, S. V., Zuloaga, K. L., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14921049
Self-citationMohammadi, E., Chojnowska, K., Bieńkowski, M., Kostecka, A., Koczkowska, M., Zmijewski, M. A., Jąkalski, M., Ingelsson, M., Filipowicz, N. H., Olszewski, P., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22671446
Mohammadi, E., Chojnowska, K., Bieńkowski, M., Kostecka, A., Koczkowska, M., Żmijewski, M. A., Jąkalski, M., Ingelsson, M., Filipowicz, N. H., Olszewski, P., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22671458
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Role of T-cell immunity in the pathophysiology of Alzheimer’s disease and other Tauopathies
Matta, K. (2024) · theses.fr (ABES) · doi:10.70675/cea4fe5ez67c3z4445z92f7z39af62ba059b
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Self-citationUnconventional functions of natural killer cells in homeostasis and disease
Anukanth, A., & Waggoner, S. N. (2026) · The Journal of Immunology · doi:10.1093/jimmun/vkag148
TTN+ macrophages are enriched in the human choroid plexus in Alzheimer’s disease
Bhatta, S., Grzybowski, A., Ortiz, G., & DiStasio, M. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117859
Mago, H. C., Besin, V., Prodjohardjono, A., Vidyanti, A. N., Ervina, W. F., Humardani, F. M., & Mulyanata, L. T. (2026) · OBM Neurobiology · doi:10.21926/obm.neurobiol.2603346
Deng, K., & Chong, W. P. (2026) · MedComm · doi:10.1002/mco2.70983
“…NK cells in the brains are predominantly cytotoxic subsets with enhanced proinflammatory profiles such as Gzmb , Ctsd , Ctsc , and systemic depletion of NK cells reduced the proinflammatory property of microglia, drastically alleviated neuroinflammation, and improved cognitive function [ 151 ].”
Natural killer T cells as therapeutic targets for neuroinflammatory disorders
Park, H. J., Lee, S. W., Kim, T.-C., Park, Y. H., Kaer, L. V., & Hong, S. (2026) · Animal Cells and Systems · doi:10.1080/19768354.2026.2746896
“1 antibodies, which deplete both NK cells and iNKT cells, improved cognitive function in these mice (Zhang et al. 2020).”
Gommerman, J. L., Akassoglou, K., Baranzini, S. E., Becher, B., Brilot, F., Castelo‐Branco, G., Dunn, S. E., Faiz, M., Flügel, A., Ghasemlou, N., et al. (2026) · Nature Reviews Neurology · doi:10.1038/s41582-026-01272-1
Metadata
- Authors
- Zhang, Y., Fung, I. T. H., Sankar, P., Chen, X., Robison, L. S., Ye, L., D’Souza, S. S., Salinero, A. E., Kuentzel, M. L., Chittur, S. V., Zhang, W., Zuloaga, K. L., & Yang, Q.
- Affiliations
- Albany Medical College (US)
- Department of Immunology and Microbial Disease, Albany Medical College , Albany, NY 12208
- University at Albany, State University of New York (US)
- Corresponding author
- Zhang, Yuanyue
- Sankar, Poornima
- Chen, Xiangyu
- Yang, Qi
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-07
- Volume
- 205
- Issue
- 2
- Pages
- 502-510
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC7343613
- OpenAlex
- W3033144109
- Cited by
- 113
- References
- 64
- Citations by year
- 2026: 13 · 2025: 25 · 2024: 22 · 2023: 20 · 2022: 27 · 2021: 6
- FWCI
- 5.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01HL137813, R01AG057782, R01NS110749)
- 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 › Neurological Disease Mechanisms and Treatments
- Keywords
- natural killer cells, Alzheimer's disease, neuroinflammation, neurogenesis, cognitive function, microglia, innate lymphoid cells, inflammatory cytokines, amyloid-beta, neurodegeneration
- MeSH terms
- Alzheimer Disease, Animals, Antibodies, Antigens, Ly, Cognition, Disease Models, Animal, Humans, Killer Cells, Natural, Lymphocyte Depletion, Mice, Transgenic, Apoptosis, Neurogenic Inflammation, Recovery of Function, Mice, Neurogenesis, NK Cell Lectin-Like Receptor Subfamily B
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