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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Discrepancies between B cell depletion studies may stem from differences in experimental models, including differences in NK cell deficiency.
“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]
The Discussion reports inconsistent findings about NK-cell function in Alzheimer’s disease and suggests that different in vitro assays may partly explain them. It does not discuss discrepancies between B-cell depletion studies or propose differences in NK-cell deficiency as their explanation (searched: B cells, B-cell depletion, NK-cell deficiency). (LLM, conf=0.74)
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“Depletion of NK cells in the 3×Tg-AD mouse model has neuroprotective effects, including attenuated neuroinflammation, enhanced neurogenesis, and improved cognitive function [65].”
Zhang, Y., Zou, M., Wu, H., Zhu, J., & Jin, T. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106710 · Cited by 69 · see citing works
“However, contrasting results have been observed in AD mouse model, where depletion of NK cells enhanced cognitive function and reduced neuroinflammation (Zhang et al., 2020b).”
ResultSelf-citationShi, M., Chu, F., Zhu, F., & Zhu, J. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-023-03003-5 · Cited by 50 · see citing works
“Similar to neutrophils, NK cells can also infiltrate the brain of the APP/PS1 mice causing Aβ pathology [115, 128, 129], however, neutrophils not only infiltrate the brain of three mouse models of AD (APP/PS1, 5 × FAD and 3 × Tg-AD mice) [130, 131], but also infiltrate the brains of AD patients.”
BackgroundMicroglia: The Hub of Intercellular Communication in Ischemic Stroke
Zhang, Y., Lian, L., Fu, R., Liu, J., Shan, X., Jin, Y., & Xu, S. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.889442 · Cited by 48 · see citing works
Self-citationQi, C., Liu, F., Zhang, W., Han, Y., Zhang, N., Liu, Q., & Li, H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1004885 · Cited by 48 · see citing works
“Although a few studies have suggested the involvement of NK cells in AD patients and mouse models (20, 21), it is still early to conclude the precise impact of NK cells on the initiation and progression of AD pathology.”
BackgroundSelf-citationD’Souza, S. S., Zhang, Y., Bailey, J. T., Fung, I. T. H., Kuentzel, M. L., Chittur, S. V., & Yang, Q. (2021) · Aging Cell · doi:10.1111/acel.13470 · Cited by 35 · see citing works
“…monocytes and Ly6G+ neutrophils were sorted by FACS. scRNA- seq was performed as we previously described (Fung et al., 2020; Harly et al., 2019; Zhang et al., 2020). scRNA- seq libraries were generated using the chromium 5’ single- cell gene expression kit (10x genomics) according to the…”
MethodSelf-citationNatural killer cells in aging and age-related diseases
Qi, C., & Liu, Q. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106156 · Cited by 38 · see citing works
“…can alleviate neuroinflammation, loss of neural progenitors and cognitive deficits in triple transgenic (3 × Tg-AD) mice, although the Aβ deposits were not significantly altered, (Zhang et al., 2020) suggesting a detrimental role of NK cells in CNS inflammation and neurodegeneration in AD (Fig.”
BackgroundNatural killer cells in the central nervous system
Ning, Z., Liu, Y., Guo, D., Lin, W., & Tang, Y. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01324-9 · Cited by 40 · see citing works
“1 antibody, researchers found no detectable changes in amyloid Aβ deposition but amelioration of microglial activation and improvement in neurogenesis and cognitive function [120].”
BackgroundThe effects of loss of Y chromosome on male health
Bruhn‐Olszewska, B., Markljung, E., Rychlicka-Buniowska, E., Sarkisyan, D., Filipowicz, N. H., & Dumanski, J. P. (2025) · Nature Reviews Genetics · doi:10.1038/s41576-024-00805-y · Cited by 37 · see citing works
“Interestingly, studies in a mouse model of Alzheimer disease have shown that natural killer cell depletion not only reduced brain inflammation but also resulted in marked improvement in cognitive function 130 .”
Alzheimer’s Disease: From Pathogenesis to Mesenchymal Stem Cell Therapy – Bridging the Missing Link
Hu, J., & Wang, X. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.811852 · Cited by 40 · see citing works
Tissue-Dependent Adaptations and Functions of Innate Lymphoid Cells
Murphy, J. M., Ngai, L., Mortha, A., & Crome, S. Q. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.836999 · Cited by 36 · see citing works
“NK cells exhibited altered expression profiles in the disease model, with higher expression of Icam1, Ctsb, Ctsc, Ccl3 and Ccl4 (56).”
BackgroundInfluentialThe role of CD56bright NK cells in neurodegenerative disorders
Rodriguez-Mogeda, C., van Ansenwoude, C. M. J., van der Molen, L. H., Strijbis, E. M. M., Mebius, R. E., & de Vries, H. E. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03040-8 · Cited by 36 · see citing works
“Recent research has demonstrated the presence of NK cells in the brains of AD patients, especially in the lep-tomeninges and CSF, and a few studies have described their presence in AD mouse models [105, 185, 188, 189].”
BackgroundTian, Y., Lu, Y., Cao, Y., Dang, C., Wang, N., Tian, K., Luo, Q., Guo, E., Luo, S., Wang, L., et al. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.919614 · Cited by 32 · see citing works
“In transgenic AD mouse models, depletion of NK cells could enhance neurogenesis, reduce neuroinflammation, and improve cognitive function, indicating that targeting NK cells might unlock novel strategies to combat AD (Zhang et al., 2020).”
BackgroundInnate and Innate-like Effector Lymphocytes in Health and Disease
Kaer, L. V., Postoak, J. L., Song, W., & Wu, L. (2022) · The Journal of Immunology · doi:10.4049/jimmunol.2200074 · Cited by 31 · see citing works
Qian, X., Liu, X., Chen, S., & Tang, H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.986346 · Cited by 31 · see citing works
“NK cell depletion can improve the cognitive function of 3xTg-AD mice by inhibiting neuroinflammation and promoting neurogenesis without influencing Ab pathology (24).”
BackgroundImmune 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 34 · see citing works
Hudson, H. R., Sun, X., & Orr, M. E. (2025) · Neurotherapeutics · doi:10.1016/j.neurot.2024.e00519 · Cited by 26 · see citing works
New Insights and Implications of Natural Killer Cells in Parkinson’s Disease
Menees, K. B., & Lee, J. (2022) · Journal of Parkinson s Disease · doi:10.3233/jpd-223212 · Cited by 25 · see citing works
“Importantly, in this study levels of amyloid- were not altered following NK cell depletion [79].”
BackgroundMethodInfluentialZhang, L., Fang, J. S., Tang, Z., & Luo, Y. (2022) · International Journal of Medical Sciences · doi:10.7150/ijms.76660 · Cited by 24 · see citing works
Walker, K. A., An, Y., Moghekar, A., Moaddel, R., Duggan, M. R., Peng, Z., Tian, Q., Pilling, L. C., Drouin, S. M., Espeland, M. A., et al. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00772-2 · Cited by 21 · see citing works
“Although peripheral T cell infiltration into the CNS has been identified as a potential driver of AD, particularly tau progression [50], whether peripheral or central NK cell activity, or NCR1 signaling in particular, influences risk for dementia remains an area of ongoing investigation [51, 52].”
BackgroundFung, I. T. H., Zhang, Y., Shin, D. S.-H., Sankar, P., Sun, X., D’Souza, S. S., Song, R., Kuentzel, M. L., Chittur, S. V., Zuloaga, K. L., et al. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02202-2 · Cited by 22 · see citing works
Self-citationSingle-cell RNA sequencing of CSF reveals neuroprotective RAC1+ NK cells in Parkinson’s disease
Guan, Q., Liu, W., Mu, K., Hu, Q., Xie, J., Cheng, L., & Wang, X. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.992505 · Cited by 21 · see citing works
“In a triple transgenic mouse model of AD (3xTg-AD), NK cells exhibit an enhanced pro-inflammatory profile, and antibody-mediated depletion of NK cells in these transgenic mice improves cognitive functions by enhancing neurogenesis and reducing neuroinflammation without affecting the levels of amyloid beta (21).”
BackgroundImmune Modulation in Alzheimer’s Disease: From Pathogenesis to Immunotherapy
Balkhi, S., Spirito, A. D., Poggi, A. D., & Mortara, L. (2025) · Cells · doi:10.3390/cells14040264 · Cited by 22 · see citing works
“Furthermore, in mouse models, NK cells exacerbate neuroinflammation and cognitive decline, while anti-NK cell treatment improves cognitive function and mitigates neuroinflammation, indicating a detrimental impact of NK cells in AD [91].”
Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer’s disease
Seplovich, G., Bouchi, Y., Vaccari, J. P. D. R., Pareja, J. C. M., Reisner, A., Blackwell, L. S., Mechref, Y. S., Wang, K., Tyndall, J. A., Tharakan, B., et al. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-00107 · Cited by 20 · see citing works
The therapeutic potential of natural killer cells in neuropathic pain
Kim, H. W., Wang, S., Davies, A. J., & Oh, S. B. (2023) · Trends in Neurosciences · doi:10.1016/j.tins.2023.05.008 · Cited by 18 · see citing works
Sirkis, D. W., Solsberg, C. W., Johnson, T. P., Bonham, L. W., Sturm, V. E., Lee, S. E., Rankin, K. P., Rosen, H. J., Boxer, A. L., Seeley, W. W., et al. (2023) · Genome Medicine · doi:10.1186/s13073-023-01205-3 · Cited by 17 · see citing works
“2, and our findings implicating CX3CR1 expression not only in NC monocytes but also in NK cells as a candidate peripheral biomarker of familial tauopathy is complemented by recent research suggesting an important yet previously unappreciated role for NK cells in a mouse model of AD [96].”
BackgroundTian, S. L., Ye, T., & Cheng, X. (2023) · Experimental Neurology · doi:10.1016/j.expneurol.2023.114505 · Cited by 19 · see citing works
Álvarez‐Sánchez, E., Carbayo, Á., Valle‐Tamayo, N., Muñoz, L., Aumatell, J., Torres, S., Rubio‐Guerra, S., Castro, J. G., Selma‐González, J., Alcolea, D. A., et al. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03347-0 · Cited by 15 · see citing works
“Until now, all studies have focused on blocking the whole population of NK cells or targeting the major population of CD56 dim NK cells, leading to conflicting findings in ALS and other neurodegenerative diseases [29–31, 37, 38].”
Lian, P., Cai, X., Yang, X., Ma, Z., Wang, C., Liu, P., Wu, Y., Cao, X., & Xu, Y. (2024) · APOPTOSIS · doi:10.1007/s10495-024-01943-8 · Cited by 15 · see citing works
“Depletion of NK cells in transgenic AD mouse models enhanced neurogenesis, reduced inflammation, and improved cognitive function [46].”
Peripheral Immune Cells Contribute to the Pathogenesis of Alzheimer’s Disease
Zhang, H., Cao, F., Zhou, Y., Wu, B., & Li, C. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04266-6 · Cited by 15 · see citing works
“1 antibody consumption of NK cells enhances neurogenesis, reduces neuroinflammation, and improves cognitive impairment in 3×Tg-AD mice [9].”
Fernando, N., Gopalakrishnan, J., Behensky, A. A., Reich, L., Liu, C., Bass, V., Bono, M. A., Montgomery, W., Pace, R. D., Mattapallil, M., et al. (2023) · bioRxiv · doi:10.1101/2023.03.18.533293 · Cited by 14 · see citing works
Zúñiga, C. H., Gallo, B. I. A., Menchaca, R., Amescua, C. A., Hong, S. S., Hui, L., Gil, M., Rhee, Y., Yoon, S., Kim, M., et al. (2025) · Alzheimer s Research & Therapy · doi:10.1186/s13195-025-01681-2 · Cited by 14 · see citing works
“…NK cell depletion can alleviate neu - roinflammation, loss of neural progenitors and cognitive deficits in triple transgenic (3 × Tg-AD) mice, although the Aβ deposits were not significantly altered [67], suggesting an inhibitory role of NK cells in CNS inflammation and neurodegeneration in AD.”
Davis, C. M., Zhang, W. H., Bah, T. M., Roese, N. E., Allen, E. M., Leung, P., Boutros, S. W., Marzulla, T., Patel, E. M., Nie, X. J., et al. (2022) · npj Aging · doi:10.1038/s41514-022-00090-1 · Cited by 14 · see citing works
“When normalized to brain volume, ventricle size was significantly larger in Tie2hsEH than WT mice (F (1, 22) 9.”
BackgroundSelf-citationThe role of peripheral innate immune cells in Alzheimer’s disease progression
Cao, Y., Tang, K., Ma, P., Zhang, R., Yang, Y., Li, T., Zhang, Y., & Peng, X. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1616939 · Cited by 13 · see citing works
Self-citationDiagnostic Model for Alzheimer’s Disease Based on PANoptosis-Related Genes
Zhang, E., Dai, F., Chen, T., Tao, L., & Shen, X. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-231103 · Cited by 13 · see citing works
“Patients with low PANscore showed higher density of T cells CD8 + , Tfh, activated NK cells, and eosinophils infiltration, all of which are involved in the progression of AD [50, 51].”
Innate lymphoid cells in neuroinflammation
Kveštak, D., Mihalić, A., Jonjić, S., & Brizić, I. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1364485 · Cited by 13 · see citing works
“In addition to autoimmune neuroinflammation, group 1 ILCs are involved in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS) (Garofalo et al., 2020; Zhang et al., 2020).”
BackgroundInfluentialRelationship between circadian genes and memory impairment caused by sleep deprivation
Ke, P., Zheng, C., Liu, F., Wu, L., Tang, Y., Wu, Y., Lv, D., Chen, H., Qian, L., Wu, X., et al. (2022) · PeerJ · doi:10.7717/peerj.13165 · Cited by 13 · see citing works
“In AD, eliminating NK cells enhances neurogenesis and reduces neuroinflammation, improving cognitive function in mice ( Zhang et al., 2020 ).”
Hu, D., Mo, X., Jihang, L., Huang, C. B., Xie, H., & Jin, L. (2023) · Aging · doi:10.18632/aging.205084 · Cited by 12 · see citing works
“NK cell depletion does not significantly affect the concentration of beta-amyloid proteins but enhances neurogenesis and reduces neuroinflammation [17].”
BackgroundApproaches for studying neuroimmune interactions in Alzheimer’s disease
Lin, C., Tian, Y., Tanzi, R. E., & Jorfi, M. (2024) · Trends in Immunology · doi:10.1016/j.it.2024.10.002 · Cited by 10 · see citing works
Size matters: the impact of nucleus size on results from spatial transcriptomics
Mohammadi, E., Chojnowska, K., Bieńkowski, M., Kostecka, A., Koczkowska, M., Zmijewski, M. A., Jąkalski, M., Ingelsson, M., Filipowicz, N. H., Olszewski, P., et al. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04129-z · Cited by 9 · see citing works
“To better understand the identified brain layers, we integrated the measured expression profiles with a previously described snRNA-seq dataset [8].”
Zhang, K., Yang, K., Yu, G., & Shi, B. (2024) · Current Alzheimer Research · doi:10.2174/0115672050353736241218054012 · Cited by 8 · see citing works
“Studies have indicated that reducing NK cells can markedly decrease neuroin-flammation, promote neurogenesis, and ameliorate cognitive impairment [66].”
Afrakoti, L. G. M. P., Moghadam, S. D., & Hadinezhad, P. (2025) · Journal of Alzheimer s Disease Reports · doi:10.1177/25424823251329188 · Cited by 9 · see citing works
“121 125 Interestingly, LFA-1 de fi ciency protects against memory loss and neuroin fl ammation.”
Zhou, Y., & Yan, R. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05111-0 · Cited by 6 · see citing works
“Interestingly, NK cells are demonstrated to exhibit a pro-inflammatory profile in 3xTg-AD mice [11], while some evidence suggests that NK cells exhibit neuroprotective effects in some situations [12, 13].”
Ying, C., & Lin, F. (2025) · NeuroImmunoModulation · doi:10.1159/000548491 · Cited by 6 · see citing works
“…NK cell depletion improved cognitive function in neurodegenerative models, highlighting their potential detrimental role in cognitive dysfunction [45]. iNKT cells, characterized by their invariant TCR (Vα24-Jα18 in humans), bridge innate and adaptive immunity through rapid cytokine production…”
Experimental procedures for flow cytometry of wild-type mouse brain: a systematic review
Sharp, R. C., Guenther, D. T., & Farrer, M. J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1281705 · Cited by 7 · see citing works
Wang, J., Huo, X., Zhou, H., Liu, H., Li, X., Lü, N., & Sun, X. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04011-z · Cited by 6 · see citing works
“Increased infiltration of peripheral NK cells has been observed in the brains of AD patients and AD mouse models [46, 47].”
The association of microbial infection and adaptive immune cell activation in Alzheimer’s disease
Clement, M. (2023) · Discovery Immunology · doi:10.1093/discim/kyad015 · Cited by 6 · see citing works
“This depletion of NK cells was also associated with a decrease in microglial proliferative capacity and rescued inflammatory cytokine production [59].”
BackgroundIba, 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) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03087-7 · Cited by 5 · see citing works
“1) decreased neuroinflammation and behavioral decline without affecting levels of Amyloid beta pathology [50].”
BackgroundZhang, Y., Ding, S., Cao, M., Zhang, S., Li, Y., Wang, Z., Jin, Y.-X., Chen, S., Wang, Y.-M., Marshall, C., et al. (2025) · Acta Pharmacologica Sinica · doi:10.1038/s41401-025-01667-8 · Cited by 5 · see citing works
“Increasing evidence indicates that multiple immune cell types are involved in the pathogenesis of AD [6, 61, 62].”
Self-citationAdvancements in Single-Cell RNA Sequencing Research for Neurological Diseases
Yang, B.-J., Hu, S.-Q., Jiang, Y.-R., Xu, L., Shu, S., & Zhang, H. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04126-3 · Cited by 4 · see citing works
“…cytotoxicity, which can rapidly induce the secretion of cytotoxic molecules and inflammatory cytokines such as cathepsins, granzymes, perforins, TNFα, and IFNγ, further destroy cells and participate in neuroinflammation, which may be related to the occurrence and development mechanism of AD [141].”
Fohner, A. E., Sitlani, C. M., Bůžková, P., Doyle, M. F., Liu, X., Bis, J. C., Fitzpatrick, A. L., Heckbert, S. R., Huber, S. A., Kuller, L. H., et al. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220091 · Cited by 5 · see citing works
“For example, higher circulating proportions of natural killer (NK) cells were apparent before AD onset and the depletion of NK cells improved cognitive function in mice [19].”
BackgroundInteraction Between Innate Lymphoid Cells and the Nervous System
Zhang, Y., Grazda, R., & Yang, Q. (2022) · Advances in experimental medicine and biology · doi:10.1007/978-981-16-8387-9_9 · Cited by 5 · see citing works
Self-citationSi, Y., Zhang, Y., & Yang, Q. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1619196 · Cited by 4 · see citing works
“For single cell RNA sequencing, CD4 and CD8 T cells were sorted from the meninges and choroid plexus of young and aged mice by fl ow cytometry analysis. scRNA-seq was performed as we previously described (11, 25, 27).”
Self-citationBringing natural killer cells to the clinic: Opportunities beyond cancer
Cayatte, M., Picant, V., Vétizou, M., & Vivier, É. (2025) · The Journal of Experimental Medicine · doi:10.1084/jem.20250612 · Cited by 4 · see citing works
Song, G., Wu, H., Chen, H., Zhang, S., Hu, Q., Lai, H., Fuller, C., Yang, G., & Chi, H. (2024) · Current Alzheimer Research · doi:10.2174/0115672050314171240527064514 · Cited by 4 · see citing works
Mechanobiological Specialization of Choroid Plexus Macrophages Defined by Titin ExpressionPreprint
Bhatta, S., Grzybowski, A., Ortiz, G., & DiStasio, M. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.20.700716 · Cited by 6 · see citing works
“A disease-associated TTN program emerges in Alzheimer’s disease Alzheimer’s dis-271 ease (AD) is increasingly recognized as a disorder involving complex neuroimmune imbal-272 ances 13 , 44 , 45 , 46 .”
Wei, H., Wu, C., Yuan, Y., & Lai, L. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1249682 · Cited by 3 · see citing works
“Likewise, NK cells were found to contribute to neuroinflammation and AD-associated cognitive decline (Zhang et al., 2020), suggesting that targeting the innate immune cells might be novel avenues for the treatment of AD (Dubois et al.”
BackgroundMAIT cell deficiency exacerbates neuroinflammation in P301S human tau transgenic mice
Zhang, Y., Yang, Z., Jiang, N., Tan, X., Jiang, P., Cao, G., & Yang, Q. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03413-7 · Cited by 3 · see citing works
Self-citationNatural killer cell immunotherapies beyond cancer
Guo, X., Chen, S., Wang, R., Ma, S., & Li, N. (2025) · Cell investigation. · doi:10.1016/j.clnves.2025.100048 · Cited by 3 · see citing works
Dinh, Q. N., Lo, C., Zhang, D. E. W., Tran, V., Hughes, T. A. G., Georgia-Sherriff, A., Diep, H., Kim, H. A., Zhang, S. R., Arce, L. J. B., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-52214-0 · Cited by 3 · see citing works
MousiPLIER: A Mouse Pathway-Level Information Extractor Model
Zhang, S., Heil, B. J., Mao, W., Chikina, M. D., Greene, C. S., & Heller, E. A. (2024) · eNeuro · doi:10.1523/eneuro.0313-23.2024 · Cited by 3 · see citing works
Natural Killer Cells in Alzheimer's Disease: From Foe to Friend
Kostić, M. S., Živković, N., Cvetanović, A., Bašić, J., & Stojanović, I. R. (2025) · European Journal of Neuroscience · doi:10.1111/ejn.70096 · Cited by 3 · see citing works
“In addition to reduced neuroinflammation, NK cell-depleted 3xTg-AD mice also displayed increased neurogenesis in the subventricular zone and hippocampal dentate gyrus and accordingly performed better on spatial memory tests compared to control 3xTg-AD mice (Zhang et al. 2020).”
InfluentialZhang, Y., Wu, J., You, G., Guo, W., Wang, Y., Yu, Z., Geng, Y., Zhong, Q., Zan, J., & Zheng, L. (2023) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2206138 · Cited by 4 · see citing works
“Considering that immune cell infiltration is associated with cognition and AD pathology [25,26], we then analyzed different immune cell populations identified between AD patients and healthy control from GSE33000.”
BackgroundSelf-citationGizowski, C., Popova, G., Shin, H., Mader, M. M.-D., Craft, W., Kong, W., Shibuya, Y., Wranik, B. J., Fu, Y. H. H., Depp, C., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.02.673859 · Cited by 4 · see citing works
Cai, Y., Huang, G., Ren, M., Chai, Y., Fu, Y., Yan, T., & Zhu, L. (2025) · Journal of Inflammation Research · doi:10.2147/jir.s499343 · Cited by 2 · see citing works
Yang, H., You, X., Yue, C., Yu, X., Yue, X., Zheng, X., Yan, X., Li, J., Bi, J., Zhang, L., et al. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251390553 · Cited by 2 · see citing works
Zhou, S., Xu, L., Dong, J., Zhang, X., Gao, W., Luo, H., & Fang, X. (2026) · Phytotherapy Research · doi:10.1002/ptr.70249 · Cited by 2 · see citing works
“However, NK cell depletion alleviated cognitive deficits without affecting Aβ deposition (Zhang, Fung, et al. 2020) (Figure 4).”
Song, J. (2022) · Clinical Nutrition Research · doi:10.7762/cnr.2022.11.3.159 · Cited by 2 · see citing works
“Several studies have mentioned that AD brain tissue shows greater activation of immune cells, such as natural killer cells [57,58], and elevated leukocyte infiltration and trafficking [59], leading to memory loss [60].”
BackgroundChen, X., Hu, F., Chi, Q., & Rao, C. (2024) · Journal of Alzheimer s Disease · doi:10.1177/13872877241295316 · Cited by 2 · see citing works
“7 Although studies suggested that NK cell impacted cognitive functions and AD progression, related research remains relatively limited needs further exploration.”
Self-citationBiomarkers for Neurodegenerative Diseases
Abdelmoaty, M. M., Lu, E., & Foster, E. G. (2024) · Springer eBooks · doi:10.1007/978-3-031-68237-7_44 · Cited by 2 · see citing works
Farris, T., Ochoa, S. G., Mohammed, M. A., Rajakaruna, H., Tonello, J. M., Kanagasabai, T., Korolkova, O. Y., Shimamoto, A., Ivanova, A. V., & Shanker, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137406 · Cited by 1 · see citing works
“On the contrary, the depletion of these reactive populations led to improved cognitive function by reducing inflammation [100,101].”
BackgroundZhang, H., Hamit, D., Li, Q., Hu, X., Li, S.-F., Xu, F., Wang, M., Bao, G.-Q., & Li, H. (2025) · Scientific Reports · doi:10.1038/s41598-024-80755-x · Cited by 1 · see citing works
“Moreover, reduced NK cell levels improve neuroinflammation and cognitive decline in a mouse model of AD 114 .”
Identification of GABBR2 as a diagnostic marker and its association with Aβ in Alzheimer's disease
Li, H., Fan, Y., Chen, C., Xu, Y., Wang, X., & Liu, W. (2025) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2025.102035 · Cited by 1 · see citing works
“Depletion of NK cells improved memory deficiency in 3xTg AD transgenic mice [45].”
White Blood Cells in Neurodegenerative Diseases in the Context of Neuroinflammation
Wełnicka, A., & Gołąb-Janowska, M. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05476-2 · Cited by 1 · see citing works
“Treatment with anti‑NK antibodies resulted in enhanced neurogenesis [72].”
Hospital-treated infection associated with Alzheimer’s disease pathology: underlying mechanisms
Barichello, T., Scaini, G., Tayyab, M., Dal-Pizzol, H. R., Petronilho, F. C., & Dal‐Pizzol, F. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03690-5 · Cited by 1 · see citing works
“In preclinical studies, the depletion of natural killer (NK) cells improved cognitive function, and microglial cells demonstrated a homeostatic-like morphology in a triple-transgenic AD mouse model (3xTg-AD) [83].”
Is amyloid beta peptide a driver of inflammaging?
Kechko, O. I., Moskalev, A. A., Franceschi, C., Mitkevich, V. A., & Makarov, A. А. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103280 · Cited by 1 · see citing works
(2022) · Journal of Medical Case Reports and Case Series · doi:10.38207/jmcrcs/2022/jan030101
Is there a role for B cells in Alzheimer's disease?
Charavner, E.-L., Fillatreau, S., & El Behi, M. (2026) · Cellular Immunology · doi:10.1016/j.cellimm.2026.105154
Size matters - the impact of nucleus size on results from spatial transcriptomicsPreprint
Mohammadi, E., Chojnowska, K., Bieńkowski, M., Kostecka, A., Koczkowska, M., Zmijewski, M. A., Jąkalski, M., Ingelsson, M., Filipowicz, N. H., Olszewski, P., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.03.31.486657
Size Matters - The Impact of Nucleus Size on Results From Spatial TranscriptomicsPreprint
Mohammadi, E., Chojnowska, K., Bieńkowski, M., Kostecka, A., Koczkowska, M., Zmijewski, M. A., Jąkalski, M., Ingelsson, M., Filipowicz, N. H., Olszewski, P., et al. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4102623
Sirkis, D. W., Solsberg, C. W., Johnson, T. P., Bonham, L. W., Sturm, V. E., Lee, S. E., Rankin, K. P., Rosen, H. J., Boxer, A. L., Seeley, W. W., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.10.28.514304
Identification and validation of PANoptosis-related genes in Alzheimer's disease
Zhou, W., Lin, H., Huang, X., & Zhou, X. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251396927
“58,59 In addition to Th17 cells, studies on A β pathological model mice and AD patients found signi fi cant increases in a large number of other peripheral innate immune cells in the CNS, including macrophages, natural killer cells and neutrophils, 60 – 62 consistent with our fi ndings.”
Mohammadi, 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.22671449
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.22671455
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.22671452
- 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
- Health Sciences › Medicine › Physiology › 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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