Peripheral cancer attenuates amyloid pathology in Alzheimer’s disease via cystatin-c activation of TREM2
Abstract
Alzheimer's disease (AD) and cancer are among the most devastating diseases worldwide. Epidemiological data indicate that the incidence of AD significantly decreases in patients with a history of cancer. However, whether and how peripheral cancer may affect AD progression is yet to be studied. Here, we find that peripheral cancer inhibits amyloid pathology and rescues cognition via secretion of cystatin-c (Cyst-C), which binds amyloid oligomers and activates triggering receptor expressed on myeloid cells 2 (TREM2) in microglia, enabling microglia to degrade the pre-existing amyloid plaques in AD mice. These effects of Cyst-C are abolished by a cell-type-specific deletion (Cx3cr1TREM2-/-) or mutation of TREM2 (TREM2R47H) or Cyst-C (Cyst-CL68Q) in microglia. Together, these findings provide significant conceptual advances into cancer neuroscience and establish therapeutic avenues that are distinct from the present amyloid-lowering strategies, aiming at degrading the existing amyloid plaques for precision-targeted AD therapy.
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Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429 · see citing works
Lecanemab in early Alzheimer's disease
van Dyck, C. H., Swanson, C. J., Aisen, P., Bateman, R. J., Chen, C., Gee, M., Kanekiyo, M., Li, D., Reyderman, L., Cohen, S., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2212948 · Cited by 5,678 · see citing works
Scheltens, P., De Strooper, B., Kivipelto, M., Holstege, H., Chételat, G., Teunissen, C. E., Cummings, J., & van der Flier, W. M. (2021) · The Lancet · doi:10.1016/s0140-6736(20)32205-4 · Cited by 5,465 · see citing works
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 · see citing works
<i>TREM2</i> Variants in Alzheimer's Disease
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211851 · Cited by 3,020 · see citing works
Tau in physiology and pathology
Wang, Y., & Mandelkow, E. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.1 · Cited by 2,251 · see citing works
Self-citationTau-mediated neurodegeneration in Alzheimer’s disease and related disorders
Ballatore, C., Lee, V. M.-Y., & Trojanowski, J. Q. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2194 · Cited by 2,174 · see citing works
Amyloid Precursor Protein Processing and Alzheimer's Disease
O'Brien, R. J., & Wong, P. C. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113613 · Cited by 2,061 · see citing works
Genetic enhancement of learning and memory in mice
Tang, Y., Shimizu, E., Dubé, G., Rampon, C., Kerchner, G. A., Zhuo, M., Liu, G., & Tsien, J. Z. (1999) · Nature · doi:10.1038/43432 · Cited by 1,867 · see citing works
Blood–brain barrier breakdown is an early biomarker of human cognitive dysfunction
Nation, D. A., Sweeney, M. D., Montagne, A., Sagare, A. P., D’Orazio, L. M., Pachicano, M., Sepehrband, F., Nelson, A. R., Buennagel, D. P., Harrington, M. G., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0297-y · Cited by 1,728 · see citing works
Donanemab in Early Alzheimer’s Disease
Mintun, M. A., Lo, A. C., Duggan Evans, C., Wessels, A. M., Ardayfio, P. A., Andersen, S. W., Shcherbinin, S., Sparks, J., Sims, J. R., Brys, M., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2100708 · Cited by 1,728 · see citing works
Alzheimer’s Disease: The Challenge of the Second Century
Holtzman, D. M., Morris, J. C., & Goate, A. M. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002369 · Cited by 1,424 · see citing works
Gamma frequency entrainment attenuates amyloid load and modifies microglia
Iaccarino, H. F., Singer, A. C., Martorell, A. J., Rudenko, A., Gao, F., Gillingham, T. Z., Mathys, H., Seo, J., Kritskiy, O., Abdurrob, F., et al. (2016) · Nature · doi:10.1038/nature20587 · Cited by 1,328 · see citing works
APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline
Montagne, A., Nation, D. A., Sagare, A. P., Barisano, G., Sweeney, M. D., Chakhoyan, A., Pachicano, M., Joe, E., Nelson, A. R., D’Orazio, L. M., et al. (2020) · Nature · doi:10.1038/s41586-020-2247-3 · Cited by 1,281 · see citing works
Edwards, D. R., Handsley, M. M., & Pennington, C. (2008) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2008.08.001 · Cited by 1,165 · see citing works
Role of tau protein in both physiological and pathological conditions
AVILA, J., LUCAS, J. J., PÉREZ, M., & HERNÁNDEZ, F. (2004) · Physiological Reviews · doi:10.1152/physrev.00024.2003 · Cited by 1,005 · see citing works
Roles of tau protein in health and disease
Guo, T., Noble, W., & Hanger, D. P. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1707-9 · Cited by 1,003 · see citing works
Amyloid β-based therapy for Alzheimer’s disease: Challenges, successes and future
Zhang, Y., Chen, H., Li, R., Sterling, K., & Song, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01484-7 · Cited by 988 · see citing works
Yeh, F. L., Wang, Y., Tom, I., Gonzalez, L. C., & Sheng, M. (2016) · Neuron · doi:10.1016/j.neuron.2016.06.015 · Cited by 943 · see citing works
Self-citationTREM2 Is a Receptor for β-Amyloid that Mediates Microglial Function
Zhao, Y., Wu, X., Li, X., Jiang, L.-L., Gui, X., Liu, Y., Sun, Y., Zhu, B., Piña-Crespo, J. C., Zhang, M., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.01.031 · Cited by 763 · see citing works
Self-citationCharacterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease
Garcia-Alloza, M., Robbins, E. M., Zhang-Nunes, S. X., Purcell, S. M., Betensky, R. A., Raju, S., Prada, C., Greenberg, S. M., Bacskai, B. J., & Frosch, M. P. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.08.017 · Cited by 744 · see citing works
Ramsden, M., Kotilinek, L., Forster, C., Paulson, J., McGowan, E., SantaCruz, K., Guimaraes, A., Yue, M., Lewis, J., Carlson, G., et al. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3279-05.2005 · Cited by 702 · see citing works
Jay, T. R., Miller, C. M., Cheng, P. J., Graham, L. C., Bemiller, S., Broihier, M. L., Xu, G., Margevicius, D., Karlo, J. C., Sousa, G. L., et al. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20142322 · Cited by 682 · see citing works
Cancer neuroscience: State of the field, emerging directions
Winkler, F., Venkatesh, H. S., Amit, M., Batchelor, T. T., Demir, İ. E., Deneen, B., Gutmann, D. H., Hervey‐Jumper, S. L., Kuner, T., Mabbott, D., et al. (2023) · Cell · doi:10.1016/j.cell.2023.02.002 · Cited by 578 · see citing works
β2 Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic Cancer
Renz, B. W., Takahashi, R., Tanaka, T., Macchini, M., Hayakawa, Y., Dantes, Z., Maurer, H. C., Chen, X., Jiang, Z., Westphalen, C. B., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2017.11.007 · Cited by 543 · see citing works
Meta-hallmarks of aging and cancer
López-Otín, C., Pietrocola, F., Roiz-Valle, D., Galluzzi, L., & Kroemer, G. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2022.11.001 · Cited by 529 · see citing works
The probabilistic model of Alzheimer disease: the amyloid hypothesis revised
Frisoni, G. B., Altomare, D., Thal, D. R., Ribaldi, F., van der Kant, R., Ossenkoppele, R., Blennow, K., Cummings, J., van Duijn, C., Nilsson, P. M., et al. (2022) · Nature Reviews Neuroscience · doi:10.1038/s41583-021-00533-w · Cited by 513 · see citing works
Heckmann, B. L., Teubner, B. J. W., Tummers, B., Boada-Romero, E., Harris, L., Yang, M., Guy, C. S., Zakharenko, S. S., & Green, D. R. (2019) · Cell · doi:10.1016/j.cell.2019.05.056 · Cited by 503 · see citing works
TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways
Wang, S., Sudan, R., Peng, V., Zhou, Y., Du, S., Yuede, C. M., Lei, T., Hou, J., Cai, Z., Cella, M., et al. (2022) · Cell · doi:10.1016/j.cell.2022.09.033 · Cited by 471 · see citing works
Söderberg, L., Johannesson, M., Nygren, P., Laudon, H., Eriksson, F., Osswald, G., Möller, C., & Lannfelt, L. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01308-6 · Cited by 444 · see citing works
Alzheimer's disease and Aβ toxicity: from top to bottom
Small, D. H., Mok, S. S., & Bornstein, J. C. (2001) · Nature reviews. Neuroscience · doi:10.1038/35086072 · Cited by 390 · see citing works
Mancusi, R. A., & Monje, M. (2023) · Nature · doi:10.1038/s41586-023-05968-y · Cited by 370 · see citing works
Progenitors from the central nervous system drive neurogenesis in cancer
Mauffrey, P., Tchitchek, N., Barroca, V., Bemelmans, A., Firlej, V., Allory, Y., Roméo, P., & Magnon, C. (2019) · Nature · doi:10.1038/s41586-019-1219-y · Cited by 356 · see citing works
Plaque formation and the intraneuronal accumulation of β‐amyloid in Alzheimer's disease
Takahashi, R. H., Nagao, T., & Gouras, G. K. (2017) · Pathology International · doi:10.1111/pin.12520 · Cited by 354 · see citing works
TREM2 deficiency impairs chemotaxis and microglial responses to neuronal injury
Mazaheri, F., Snaidero, N., Kleinberger, G., Madore, C., Daria, A., Werner, G., Krasemann, S., Capell, A., Trümbach, D., Wurst, W., et al. (2017) · The EMBO Reports · doi:10.15252/embr.201743922 · Cited by 351 · see citing works
Intraneuronal Aβ accumulation and origin of plaques in Alzheimer's disease
Gouras, G. K., Almeida, C. G., & Takahashi, R. H. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.05.022 · Cited by 338 · see citing works
Cancer hallmarks intersect with neuroscience in the tumor microenvironment
Hanahan, D., & Monje, M. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.012 · Cited by 325 · see citing works
Neuropathology and biochemistry of Aβ and its aggregates in Alzheimer’s disease
Thal, D. R., Walter, J., Saido, T. C., & Fändrich, M. (2015) · Acta Neuropathologica · doi:10.1007/s00401-014-1375-y · Cited by 319 · see citing works
Biochemistry and Clinical Role of Human Cystatin C
Mussap, M., & Plebani, M. (2004) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408360490504934 · Cited by 316 · see citing works
Altered microglial response to Aβ plaques in APPPS1-21 mice heterozygous for TREM2
Ulrich, J. D., Finn, M. B., Wang, Y., Shen, A., Mahan, T. E., Jiang, H., Stewart, F. R., Piccio, L., Colonna, M., & Holtzman, D. M. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-20 · Cited by 302 · see citing works
Self-citationBACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice
Ohno, M., Cole, S. L., Yasvoina, M., Zhao, J., Citron, M., Berry, R., Disterhoft, J. F., & Vassar, R. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.12.008 · Cited by 290 · see citing works
Activation of Wnt/β-catenin pathway mitigates blood–brain barrier dysfunction in Alzheimer’s disease
Wang, Q., Huang, X., Su, Y., Yin, G., Wang, S., Yu, B., Li, H., Qi, J., Chen, H., Zeng, W., et al. (2022) · Brain · doi:10.1093/brain/awac236 · Cited by 219 · see citing works
Self-citationKim, J., Jiang, H., Park, S., Eltorai, A. E. M., Stewart, F. R., Yoon, H., Basak, J. M., Finn, M. B., & Holtzman, D. M. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3773-11.2011 · Cited by 199 · see citing works
Sunderland, T., Mirza, N., Putnam, K. T., Linker, G., Bhupali, D., Durham, R., Soares, H., Kimmel, L., Friedman, D., Bergeson, J., et al. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.07.021 · Cited by 179 · see citing works
Cystatin C modulates cerebral β-amyloidosis
Kaeser, S. A., Herzig, M. C., Coomaraswamy, J., Kilger, E., Selenica, M. B., Winkler, D. T., Staufenbiel, M., Levy, E., GRUBB, A. O., & Jucker, M. (2007) · Nature Genetics · doi:10.1038/ng.2007.23 · Cited by 172 · see citing works
Ochieng, J., & Chaudhuri, G. (2010) · Journal of Health Care for the Poor and Underserved · doi:10.1353/hpu.0.0257 · Cited by 161 · see citing works
Cerebrovascular pathology during the progression of experimental Alzheimer's disease
Giannoni, P., Arango-Lievano, M., das Neves, I., Rousset, M.-C., Baranger, K., Rivera, S., Jeanneteau, F. D., Claeysen, S., & Marchi, N. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.01.001 · Cited by 146 · see citing works
Chronic TREM2 activation exacerbates Aβ-associated tau seeding and spreading
Jain, N., Lewis, C. A., Ulrich, J. D., & Holtzman, D. M. (2023) · Journal of Experimental Medicine · doi:10.1084/jem.20220654 · Cited by 146 · see citing works
Ellwanger, D. C., Wang, S., Brioschi, S., Shao, Z., Green, L. B., Case, R. B., Yoo, D., Weishuhn, D., Rathanaswami, P., Bradley, J., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2017742118 · Cited by 143 · see citing works
Cystatin C in aging and in Alzheimer’s disease
Mathews, P. M., & Levy, E. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.06.003 · Cited by 133 · see citing works
Insulin-degrading enzyme: new therapeutic target for diabetes and Alzheimer’s disease?
Pivovarova‐Ramich, O., Höhn, A., Grune, T., Pfeiffer, A. F. H., & Rudovich, N. N. (2016) · Annals of Medicine · doi:10.1080/07853890.2016.1197416 · Cited by 132 · see citing works
Lanni, C., Masi, M., Racchi, M., & Govoni, S. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-0760-2 · Cited by 130 · see citing works
Ospina-Romero, M., Glymour, M. M., Hayes-Larson, E., Mayeda, E. R., Graff, R. E., Brenowitz, W. D., Ackley, S. F., Witte, J. S., & Kobayashi, L. C. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.25515 · Cited by 124 · see citing works
Schlepckow, K., Morenas‐Rodríguez, E., Hong, S. Y., & Haass, C. (2023) · The Lancet Neurology · doi:10.1016/s1474-4422(23)00247-8 · Cited by 121 · see citing works
Calsyntenin-1 mediates axonal transport of the amyloid precursor protein and regulates A production
Vagnoni, A., Perkinton, M. S., Gray, E. H., Francis, P. T., Noble, W. J., & Miller, C. C. J. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds109 · Cited by 117 · see citing works
Association of cancer and Alzheimer's disease risk in a national cohort of veterans
Frain, L., Swanson, D., Cho, K., Gagnon, D., Lu, K. P., Betensky, R. A., & Driver, J. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2017.04.012 · Cited by 115 · see citing works
Neumann, U., Rueeger, H., Machauer, R., Veenstra, S. J., Lueoend, R. M., Tintelnot-Blomley, M., Laue, G., Beltz, K., Vogg, B., Schmid, P., et al. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0033-8 · Cited by 113 · see citing works
Wheal, H. V., Chen, Y., Mitchell, J., Schachner, M., Maerz, W., Wieland, H., van Rossum, D., & Kirsch, J. (1998) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00026-4 · Cited by 93 · see citing works
Intraneuronal Aβ accumulation and neurodegeneration: Lessons from transgenic models
Wirths, O., & Bayer, T. A. (2012) · Life Sciences · doi:10.1016/j.lfs.2012.02.001 · Cited by 91 · see citing works
Myelin changes at the early stage of 5XFAD mice
Gu, L., Wu, D., Tang, X., Qi, X., Li, X., Bai, F., Chen, X., Ren, Q., & Zhang, Z. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2017.12.013 · Cited by 87 · see citing works
Self-citationBekris, L. M., Millard, S. P., Galloway, N. M., Vuletic, S., Albers, J. J., Li, G., Galasko, D. R., DeCarli, C., Farlow, M. R., Clark, C. M., et al. (2008) · Journal of Alzheimer's Disease · doi:10.3233/jad-2008-13303 · Cited by 85 · see citing works
Zhao, Y., Zheng, Q., Hong, Y., Gao, Y., Hu, J., Lang, M., Zhang, H., Zhou, Y., Luo, H., Zhang, X., et al. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01352-1 · Cited by 84 · see citing works
Self-citationLi, X., Chen, W., Pan, K., Li, H., Pang, P., Guo, Y., Shu, S., Cai, Y., Pei, L., Liu, D., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0207-0 · Cited by 83 · see citing works
Self-citationAssociations between cancer and Alzheimer's disease in a U.S. Medicare population
Freedman, D. M., Wu, J., Chen, H., Kuncl, R. W., Enewold, L., Engels, E. A., Freedman, N. D., & Pfeiffer, R. M. (2016) · Cancer Medicine · doi:10.1002/cam4.850 · Cited by 75 · see citing works
Inverse Correlation Between Alzheimer’s Disease and Cancer: Short Overview
Zabłocka, A., Kazana, W., Sochocka, M., Stańczykiewicz, B., Janusz, M., Leszek, J., & Orzechowska, B. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02544-1 · Cited by 73 · see citing works
Galvão, F., Grokoski, K. C., da Silva, B. B., Lamers, M. L., & Siqueira, I. R. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.11.007 · Cited by 66 · see citing works
Lidia de, B. A. R. I., Atlante, A., Armeni, T., & Kalapos, M. P. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100915 · Cited by 66 · see citing works
Wu, D., Tang, X., Gu, L., Li, X., Qi, X., Bai, F., Chen, X., Wang, J., Ren, Q., & Zhang, Z. (2018) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12809 · Cited by 64 · see citing works
Self-citationMultiple cancer cell types release LIF and Gal3 to hijack neural signals
Xu, Q., Cao, Y., Kong, F., Liu, J., Chen, X., Zhao, Y., Lai, C., Zhou, X., Hu, H., Fu, W., et al. (2024) · Cell Research · doi:10.1038/s41422-024-00946-z · Cited by 61 · see citing works
Self-citationMolecularly defined and functionally distinct cholinergic subnetworks
Li, X., Yu, H., Zhang, B., Li, L., Chen, W., Yu, Q., Huang, X., Xiao, K., Wang, Y., Jing, W., et al. (2022) · Neuron · doi:10.1016/j.neuron.2022.08.025 · Cited by 58 · see citing works
Self-citationBai, N., Li, N., Cheng, R., Guan, Y., Zhao, X., Song, Z., Xu, H., Yi, F., Jiang, B., Li, X., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111062 · Cited by 56 · see citing works
Self-citationPresenilin-1 (PSEN1) Mutations: Clinical Phenotypes beyond Alzheimer’s Disease
Yang, Y., Bagyinszky, E., & An, S. S. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24098417 · Cited by 56 · see citing works
Specific Eph receptor-cytoplasmic effector signaling mediated by SAM–SAM domain interactions
Wang, Y., Shang, Y., Li, J., et al. (2018) · eLife · doi:10.7554/elife.35677 · Cited by 52 · see citing works
Self-citationPlá, V., Paco, S., Ghézali, G., Ciria, V., Pozas, E., Ferrer, I., & Aguado, F. (2012) · Brain Pathology · doi:10.1111/j.1750-3639.2012.00644.x · Cited by 50 · see citing works
Interaction between Oligomers of Stefin B and Amyloid-β in Vitro and in Cells
Škerget, K., Taler‐Verčič, A., Bavdek, A., Hodnik, V., Čeru, S., Tušek‐Žnidarič, M., Kumm, T., Pitsi, D., Pompe‐Novak, M., Palumaa, P., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.024620 · Cited by 44 · see citing works
Karanth, S. D., Katsumata, Y., Nelson, P. T., Fardo, D. W., McDowell, J. K., Schmitt, F. A., Kryscio, R. J., Browning, S. R., Braithwaite, D., Arnold, S. M., et al. (2022) · Brain · doi:10.1093/brain/awac035 · Cited by 41 · see citing works
A circuit of mossy cells controls the efficacy of memory retrieval by Gria2I inhibition of Gria2
Li, X., Chen, W., Yu, Q., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108741 · Cited by 37 · see citing works
Self-citationNon-melanoma skin cancer and risk of Alzheimer’s disease and all-cause dementia
Schmidt, S. A. J., Ording, A. G., Horváth–Puhó, E., Sørensen, H. T., & Henderson, V. W. (2017) · PLoS ONE · doi:10.1371/journal.pone.0171527 · Cited by 36 · see citing works
Investigating the association between cancer and dementia risk: a longitudinal cohort study
Zhang, D., Ou, Y., Liu, Y., Ma, Y., Tan, L., Feng, J., Cheng, W., & Yu, J. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-01090-9 · Cited by 36 · see citing works
Perlenfein, T. J., Mehlhoff, J. D., & Murphy, R. M. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.786558 · Cited by 31 · see citing works
Regulation of glial development by cystatin C
Hasegawa, A., Naruse, M., Hitoshi, S., Iwasaki, Y., Takebayashi, H., & Ikenaka, K. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04169.x · Cited by 30 · see citing works
Liu, P., Paulson, J. B., Forster, C. L., Shapiro, S. L., Ashe, K. H., & Zahs, K. R. (2015) · PLoS ONE · doi:10.1371/journal.pone.0126317 · Cited by 28 · see citing works
Wang, X.-F., Liu, D.-X., Liang, Y., Xing, L.-L., Zhao, W.-H., Qin, X.-X., Shang, D.-S., Li, B., Fang, W.-G., Cao, L., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0161093 · Cited by 24 · see citing works
BACE-1 Inhibitors Targeting Alzheimer's Disease
Monteiro, K. L. C., Alcântara, M. G. D. S., Freire, N. M. L., Brandão, E. M., do Nascimento, V. L., Viana, L. M. D. S., de Aquino, T. M., & da Silva‐Júnior, E. F. (2023) · Current Alzheimer Research · doi:10.2174/1567205020666230612155953 · Cited by 23 · see citing works
Park, M. H., Yun, H., Hwang, C. J., Park, S. I., Han, S., Hwang, D. Y., Yoon, D., Kim, S., & Hong, J. T. (2017) · Theranostics · doi:10.7150/thno.21408 · Cited by 22 · see citing works
Synaptic dysfunction of Aldh1a1 neurons in the ventral tegmental area causes impulsive behaviors
Li, X., Chen, W., Huang, X., Jing, W., Zhang, T., Yu, Q., Yu, H., Li, H., Tian, Q., Ding, Y., et al. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00494-9 · Cited by 20 · see citing works
Self-citationPotential Therapeutic Implications of Gelsolin in Alzheimer's Disease
Ji, L., Zhao, X., & Hua, Z. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-141548 · Cited by 19 · see citing works
Zhang, J., Chen, Y., Zhao, Y., Wang, P., Ding, H., Liu, C., Lyu, J., & Le, W. (2023) · Neuroscience Bulletin · doi:10.1007/s12264-023-01145-3 · Cited by 19 · see citing works
Weaver, D. F. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13165 · Cited by 17 · see citing works
Lau, S., Wu, W., Seo, H., Fu, A. K. Y., & Ip, N. Y. (2021) · STAR Protocols · doi:10.1016/j.xpro.2020.100265 · Cited by 17 · see citing works
Li, Q., Li, B., Liu, L., Wang, K.-J., Liu, M., Deng, Y., Li, Z., Zhao, W., Wu, L., Chen, Y., et al. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03119-2 · Cited by 15 · see citing works
Akbaba, H., Erel‐Akbaba, G., & Şentürk, Ş. (2021) · Nanomedicine · doi:10.2217/nnm-2020-0412 · Cited by 14 · see citing works
Cancer and Aging: A Complex Biological Association
Navarrete‐Reyes, A. P., Soto‐Pérez‐de‐Celis, E., & Hurria, A. (2016) · Revista de investigaci�n Cl�nica · doi:10.1016/s0034-8376(25)00203-7 · Cited by 13 · see citing works
Trem2 Enhances Demyelination in the Csf1r+/− Mouse Model of Leukoencephalopathy
Biundo, F., Chiţu, V., Gökhan, Ş., Chen, E., Oppong‐Asare, J., & Stanley, E. R. (2023) · Biomedicines · doi:10.3390/biomedicines11082094 · Cited by 8 · see citing works
Development of an immunoassay for the detection of cystatin C dimers
Hyytiä, H., Ristiniemi, N., Airas, L. M., et al. (2010) · Journal of Immunological Methods · doi:10.1016/j.jim.2010.02.014 · Cited by 3 · see citing works
Tejera, C. H., Ware, E. B., Hicken, M. T., et al. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.053278 · Cited by 1 · see citing works
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Tumor-derived cystatin C enables amyloid clearance
Zambelas, J., Huang, Y., Zhao, H., & Wong, S. T. C. (2026) · Trends in Immunology · doi:10.1016/j.it.2026.02.007 · Cited by 1 · see citing works
- Authors
- Li, X., Tang, X., Zeng, J., Duan, L., Hou, Z., Li, L., Guo, Y., Chai, C., Liu, J., Wang, Y., Zhu, L.-Q., Li, H., Zhang, T., Wang, Y., He, A., & Lu, Y.
- Affiliations
- Huazhong University of Science and Technology (CN)
- Wuhan Union Hospital (CN)
- Tongji Hospital (CN)
- Corresponding author
- Lu, Youming
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2026-02
- Volume
- 189
- Issue
- 3
- Pages
- 853-871.e31
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W7125416134
- Semantic Scholar
- 21eccc27dfb384cd3c8c2de521adf2069162608b
- Cited by
- 21
- References
- 96
- Citations by year
- 2026: 21
- FWCI
- 82.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Huazhong University of Science and Technology
- National Natural Science Foundation of China (32421003, 82430044, 82271486)
- Ministry of Education of the People's Republic of China
- Wuhan Union Hospital
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, cystatin C, TREM2, microglia, amyloid plaques, amyloid oligomers, amyloid clearance, CX3CR1, cancer neuroscience
- MeSH terms
- CX3C Chemokine Receptor 1, Alzheimer Disease, Amyloid, Animals, Disease Models, Animal, Humans, Male, Membrane Glycoproteins, Mice, Inbred C57BL, Receptors, Immunologic, Amyloid beta-Peptides, Microglia, Mice, Cystatin C, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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