Co-expression network analysis of human tau-transgenic mice reveals protein modules associated with tau-induced pathologies
Open accessAbstract
Abnormally accumulated tau protein aggregates are one of the hallmarks of neurodegenerative diseases, including Alzheimer's disease (AD). In order to investigate proteomic alteration driven by tau aggregates, we implemented quantitative proteomics to analyze disease model mice expressing human MAPT P301S transgene (hTau-Tg) and quantified more than 9,000 proteins in total. We applied the weighted gene co-expression analysis (WGCNA) algorithm to the datasets and explored protein co-expression modules that were associated with the accumulation of tau aggregates and were preserved in proteomes of AD brains. This led us to identify four modules with functions related to neuroinflammatory responses, mitochondrial energy production processes (including the tricarboxylic acid cycle and oxidative phosphorylation), cholesterol biosynthesis, and postsynaptic density. Furthermore, a phosphoproteomics study uncovered phosphorylation sites that were highly correlated with these modules. Our datasets represent resources for understanding the molecular basis of tau-induced neurodegeneration, including AD.
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WGCNA enhanced network granularity by identifying modules of highly co-expressed genes, offering biologically relevant insights into co-regulated pathways implicated in AD.
“Subsequently, methods such as Weighted Gene Co-expression Network Analysis (WGCNA) enhanced network granularity by identifying modules of highly co-expressed genes, offering biologically relevant insights into co-regulated pathways implicated in AD244,299.”
From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [244]
The Introduction describes WGCNA as organizing highly co-expressed proteins into modules that can be linked to AD-related traits. The Results report protein modules associated with tau pathology, and the Discussion says four were preserved in AD brains. The cited study analyzed proteins, not modules of co-expressed genes as the citing sentence states. (LLM, conf=0.85)
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Cites
Cytoscape: A software Environment for integrated models of biomolecular interaction networks
Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., & Ideker, T. (2003) · Genome Research · doi:10.1101/gr.1239303 · Cited by 51,888 · see citing works
WGCNA: an R package for weighted correlation network analysis
Langfelder, P., & Horvath, S. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-559 · Cited by 27,252 · see citing works
Szklarczyk, D., Gable, A. L., Lyon, D., Junge, A., Wyder, S., Huerta-Cepas, J., Simonovic, M., Doncheva, N. T., Morris, J. H., Bork, P., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gky1131 · Cited by 17,749 · see citing works
Cox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855 · see citing works
The Perseus computational platform for comprehensive analysis of (prote)omics data
Tyanova, S., Temu, T., Sinitcyn, P. G., Carlson, A., Hein, M. Y., Geiger, T., Mann, M., & Cox, J. (2016) · Nature Methods · doi:10.1038/nmeth.3901 · Cited by 7,977 · see citing works
Rappsilber, J., Mann, M., & Ishihama, Y. (2007) · Nature Protocols · doi:10.1038/nprot.2007.261 · Cited by 4,641 · see citing works
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204 · see citing works
Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes
Kwon, H. S., & Koh, S.-H. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00221-2 · Cited by 2,595 · 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
Nelson, P. T., Alafuzoff, I., Bigio, E. H., Bouras, C., Braak, H., Cairns, N. J., Castellani, R. J., Crain, B. J., Davies, P., Tredici, K. D., et al. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31825018f7 · Cited by 2,050 · see citing works
Li, Y., Xu, S., Mihaylova, M. M., Zheng, B., Hou, X., Jiang, B., Park, O., Luo, Z., Lefai, É., Shyy, J. Y.-J., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.03.009 · Cited by 1,788 · see citing works
Hornbeck, P. V., Kornhauser, J. M., Tkachev, S., Zhang, B., Skrzypek, E., Murray, B. W., Latham, V. M., & Sullivan, M. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr1122 · Cited by 1,636 · see citing works
McAlister, G. C., Nusinow, D. P., Jedrychowski, M. P., Wühr, M., Huttlin, E. L., Erickson, B. K., Rad, R., Haas, W., & Gygi, S. P. (2014) · Analytical Chemistry · doi:10.1021/ac502040v · Cited by 1,263 · see citing works
Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer’s disease
Giannakopoulos, P., Herrmann, F. R., Bussière, T., Bouras, C., Kövari, E., Perl, D. P., Morrison, J. H., Gold, G., & Hof, P. R. (2003) · Neurology · doi:10.1212/01.wnl.0000063311.58879.01 · Cited by 1,118 · see citing works
Middeldorp, J., & Hol, E. M. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.01.005 · Cited by 1,080 · see citing works
Johnson, E. C. B., Dammer, E. B., Duong, D. M., Ping, L., Zhou, M., Yin, L., Higginbotham, L. A., Guajardo, A., White, B., Troncoso, J. C., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0815-6 · Cited by 1,001 · see citing works
Linking lipids to Alzheimer's disease: cholesterol and beyond
Di Paolo, G., & Kim, T.-W. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3012 · Cited by 972 · see citing works
Cell type- and brain region-resolved mouse brain proteome
Sharma, K., Schmitt, S., Bergner, C. G., Tyanova, S., Kannaiyan, N., Manrique-Hoyos, N., Kongi, K., Cantuti, L., Hanisch, U.-K., Philips, M.-A., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4160 · Cited by 871 · see citing works
Allen, B., Ingram, E., Takao, M., Smith, M. J., Jakes, R., Virdee, K., Yoshida, H., Holzer, M., Craxton, M., Emson, P. C., et al. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-21-09340.2002 · Cited by 746 · see citing works
jPOSTrepo: an international standard data repository for proteomes
Okuda, S., Watanabe, Y., Moriya, Y., Kawano, S., Yamamoto, T., Matsumoto, M., Takami, T., Kobayashi, D., Araki, N., Yoshizawa, A. C., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw1080 · Cited by 695 · see citing works
Rhein, V., Song, X., Wiesner, A., Ittner, L. M., Baysang, G., Meier, F., Ozmen, L., Bluethmann, H., Dröse, S., Brandt, U., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905529106 · Cited by 655 · see citing works
Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer’s Disease Progression
Bai, B., Wang, X., Li, Y., Chen, P.-C., Yu, K., Dey, K. K., Yarbro, J. M., Han, X., Lutz, B. M., Rao, S., et al. (2020) · Neuron · doi:10.1016/j.neuron.2019.12.015 · Cited by 632 · cited 1× · see citing works
“Phosphoproteomics identifies changed phosphorylation sites associated with tau accumulation Aberrant phosphorylation, such as the hyperphosphorylation of tau protein, plays a key role in AD pathology (Bai et al., 2020; Morshed et al., 2020; Perluigi et al., 2016; Zhang et al., 2019).”
BackgroundMitochondrial dysfunction in neurodegenerative diseases
Beal, M. F. (1998) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(98)00114-5 · Cited by 608 · see citing works
Dejanovic, B., Huntley, M. A., De Mazière, A., Meilandt, W. J., Wu, T., Srinivasan, K., Jiang, Z., Gandham, V., Friedman, B. A., Ngu, H., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.014 · Cited by 575 · see citing works
Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease
Roy, E. R., Wang, B., Wan, Y.-W., Chiu, G., Cole, A., Yin, Z., Propson, N. E., Xu, Y., Jankowsky, J. L., Liu, Z., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci133737 · Cited by 563 · see citing works
Reactive Glia not only Associates with Plaques but also Parallels Tangles in Alzheimer’s Disease
Serrano-Pozo, A., Mielke, M. L., Gómez-Isla, T., Betensky, R. A., Growdon, J. H., Frosch, M. P., & Hyman, B. T. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.05.047 · Cited by 488 · see citing works
Seyfried, N. T., Dammer, E. B., Swarup, V., Nandakumar, D., Duong, D. M., Yin, L., Deng, Q., Nguyen, T., Hales, C. M., Wingo, T., et al. (2017) · Cell Systems · doi:10.1016/j.cels.2016.11.006 · Cited by 477 · see citing works
Precision proteomics: The case for high resolution and high mass accuracy
Mann, M., & Kelleher, N. L. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800788105 · Cited by 450 · see citing works
Proteomic and functional analyses reveal a mitochondrial dysfunction in P301L tau transgenic mice
David, D. C., Hauptmann, S., Scherping, I., Schuessel, K., Keil, U., Rizzu, P., Ravid, R., Dröse, S., Brandt, U., Müller, W. E., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500356200 · Cited by 447 · see citing works
Exercise plasma boosts memory and dampens brain inflammation via clusterin
De Miguel, Z., Khoury, N., Betley, M. J., Lehallier, B., Willoughby, D., Olsson, N., Yang, A. C., Hahn, O., Lu, N., Vest, R. T., et al. (2021) · Nature · doi:10.1038/s41586-021-04183-x · Cited by 422 · see citing works
Enlightening the Postsynaptic Density
Ziff, E. B. (1997) · Neuron · doi:10.1016/s0896-6273(00)80409-2 · Cited by 381 · see citing works
Mitochondrial dysfunction in neurodegenerative diseases and drug targets via apoptotic signaling
Wu, Y., Chen, M., & Jiang, J. (2019) · Mitochondrion · doi:10.1016/j.mito.2019.07.003 · Cited by 378 · see citing works
Physical Activity and Cognitive Vitality
Prakash, R. S., Voss, M. W., Erickson, K. I., & Kramer, A. F. (2015) · Annual Review of Psychology · doi:10.1146/annurev-psych-010814-015249 · Cited by 376 · see citing works
van der Kant, R., Langness, V. F., Herrera, C. M., Williams, D. A., Fong, L. K., Leestemaker, Y., Steenvoorden, E., Rynearson, K. D., Brouwers, J. F., Helms, J. B., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2018.12.013 · Cited by 350 · see citing works
Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues
Lundby, A., Secher, A., Lage, K., Nordsborg, N. B., Dmytriyev, A., Lundby, C., & Olsen, J. V. (2012) · Nature Communications · doi:10.1038/ncomms1871 · Cited by 341 · see citing works
Navarrete-Perea, J., Yu, Q., Gygi, S. P., & Paulo, J. A. (2018) · Journal of Proteome Research · doi:10.1021/acs.jproteome.8b00217 · Cited by 339 · see citing works
Plubell, D. L., Wilmarth, P. A., Zhao, Y., Fenton, A. M., Minnier, J., Reddy, A. P., Klimek, J. E., Yang, X., David, L. L., & Pamir, N. (2017) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m116.065524 · Cited by 337 · see citing works
AMPK-Mediated Regulation of Lipid Metabolism by Phosphorylation
Wang, Q., Liu, S., Zhai, A., Zhang, B., & Tian, G. (2018) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b17-00724 · Cited by 315 · see citing works
Absence of CX3CR1 impairs the internalization of Tau by microglia
Bolós, M., Llorens-Martín, M., Perea, J. R., Jurado-Arjona, J., Rábano, A., Hernández, F., & Avila, J. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0200-1 · Cited by 231 · see citing works
Wingo, A. P., Dammer, E. B., Breen, M. S., Logsdon, B. A., Duong, D. M., Troncosco, J. C., Thambisetty, M., Beach, T. G., Serrano, G. E., Reiman, E. M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09613-z · Cited by 211 · cited 1× · see citing works
“Furthermore, some of the OXPHOS proteins including NDUFA10, one of the hub proteins, were shown to be associated with cognitive stability in a proteomic study of human brain (Wingo et al., 2019).”
BackgroundGibson, G. E., Blass, J. P., Beal, M. F., & Bunik, V. I. (2005) · Molecular Neurobiology · doi:10.1385/mn:31:1-3:043 · Cited by 180 · see citing works
Zhang, Q., Ma, C., Gearing, M., Wang, P. G., Chin, L.-S., & Li, L. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0524-2 · Cited by 165 · see citing works
Iwagami, M., Qizilbash, N., Gregson, J., Douglas, I., Johnson, M., Pearce, N., Evans, S., & Pocock, S. (2021) · The Lancet Healthy Longevity · doi:10.1016/s2666-7568(21)00150-1 · Cited by 161 · see citing works
Tau Oligomers and Fibrils Induce Activation of Microglial Cells
Morales, I., Jiménez, J. M., Mancilla, M., & Maccioni, R. B. (2013) · Journal of Alzheimer’s Disease · doi:10.3233/jad-131843 · Cited by 160 · see citing works
Cholesterol metabolism in Huntington disease
Karasinska, J. M., & Hayden, M. R. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2011.132 · Cited by 154 · see citing works
Contribution of Tau Pathology to Mitochondrial Impairment in Neurodegeneration
Maria Jose Perez, J., Jara, C., & Quintanilla, R. A. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00441 · Cited by 153 · see citing works
cAMP-PKA phosphorylation of tau confers risk for degeneration in aging association cortex
Carlyle, B. C., Nairn, A. C., Wang, M., Yang, Y., Jin, L. E., Simen, A. A., Ramos, B. P., Bordner, K. A., Craft, G. E., Davies, P., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1322360111 · Cited by 139 · see citing works
The Postsynaptic Density: There Is More than Meets the Eye
Dosemeci, A., Weinberg, R. J., Reese, T. S., & Tao-Cheng, J.-H. (2016) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2016.00023 · Cited by 138 · see citing works
The post-genomic era of interactive proteomics: Facts and perspectives
Auerbach, D., Thaminy, S., Hottiger, M. O., & Štagljar, I. (2002) · PROTEOMICS · doi:10.1002/1615-9861(200206)2:6 · Cited by 134 · see citing works
Tau drives translational selectivity by interacting with ribosomal proteins
Koren, S. A., Hamm, M. J., Meier, S. E., Weiss, B. E., Nation, G. K., Chishti, E. A., Arango, J. P., Chen, J., Zhu, H., Blalock, E. M., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-01970-9 · Cited by 122 · see citing works
AMP-activated protein kinase modulates tau phosphorylation and tau pathology in vivo
Domise, M., Didier, S., Marinangeli, C., Zhao, H., Chandakkar, P., Buée, L., Viollet, B., Davies, P., Marambaud, P., & Vingtdeux, V. (2016) · Scientific Reports · doi:10.1038/srep26758 · Cited by 120 · see citing works
Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau
Rayaprolu, S., Higginbotham, L., Bagchi, P., Watson, C. M., Zhang, T., Levey, A. I., Rangaraju, S., & Seyfried, N. T. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-020-00840-3 · Cited by 118 · cited 2× · see citing works
“1 ll OPEN ACCESS and tangle deposition (Rayaprolu et al., 2021).”
MethodIn vivo brain GPCR signaling elucidated by phosphoproteomics
Liu, J. J., Sharma, K., Zangrandi, L., Chen, C., Humphrey, S. J., Chiu, Y.-T., Spetea, M., Liu‐Chen, L., Schwarzer, C., & Mann, M. (2018) · Science · doi:10.1126/science.aao4927 · Cited by 118 · see citing works
Phosphorylation Signaling in APP Processing in Alzheimer’s Disease
Zhang, T., Chen, D., & Lee, T. H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms21010209 · Cited by 114 · see citing works
Deficits in a tricarboxylic acid cycle enzyme in brains from patients with Parkinson’s disease
Gibson, G. E., Kingsbury, A. E., Xu, H., LINDSAY, J. G., Daniel, S. E., Föster, O., Lees, A. J., & Blass, J. P. (2003) · Neurochemistry International · doi:10.1016/s0197-0186(02)00225-5 · Cited by 108 · see citing works
Frontal Lobe Dysfunction in Progressive Supranuclear Palsy
Albers, D. S., Augood, S. J., Park, L. C. H., Browne, S. E., Martin, D. M., Adamson, J. L., Hutton, M., Standaert, D. G., Vonsattel, J. P., Gibson, G. E., et al. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.740878.x · Cited by 107 · see citing works
Yoon, W. H., Sandoval, H., Nagarkar-Jaiswal, S., Jaiswal, M., Yamamoto, S., Haelterman, N. A. T., Putluri, N., Putluri, V., Sreekumar, A., Tos, T., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.11.038 · Cited by 106 · see citing works
Redjems-Bennani, N., Jeandel, C., Lefebvre, E., Blain, H., Vidailhet, M., & Guéant, J. (1998) · Gerontology · doi:10.1159/000022031 · Cited by 99 · see citing works
Marzia Perluigi, A., Barone, E., Domenico, F. D., & Butterfield, D. A. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.07.005 · Cited by 85 · see citing works
Mitochondrial impairment in the cerebellum of the patients with progressive supranuclear palsy
Park, L. C. H., Albers, D. S., Xu, H., LINDSAY, J. G., Beal, M. F., & Gibson, G. E. (2001) · Journal of Neuroscience Research · doi:10.1002/jnr.10062 · Cited by 83 · see citing works
Tau at the interface between neurodegeneration and neuroinflammation
Didonna, A. (2020) · Genes & Immunity · doi:10.1038/s41435-020-00113-5 · Cited by 82 · see citing works
Adachi, J., Hashiguchi, K., Nagano, M., Sato, M., Sato, A., Fukamizu, K., Ishihama, Y., & Tomonaga, T. (2016) · Analytical Chemistry · doi:10.1021/acs.analchem.6b01232 · Cited by 81 · see citing works
Yu, S., Kyriakidou, P., & Cox, J. (2020) · Journal of Proteome Research · doi:10.1021/acs.jproteome.0c00209 · Cited by 80 · see citing works
A Primer on Concepts and Applications of Proteomics in Neuroscience
Hosp, F., & Mann, M. (2017) · Neuron · doi:10.1016/j.neuron.2017.09.025 · Cited by 77 · see citing works
Gong, Y., & Lippa, C. F. (2010) · American Journal of Alzheimer's Disease & Other Dementias® · doi:10.1177/1533317510382893 · Cited by 76 · see citing works
Integrated analysis of the aging brain transcriptome and proteome in tauopathy
Mangleburg, C. G., Wu, T., Yalamanchili, H. K., Guo, C., Hsieh, Y.-C., Duong, D. M., Dammer, E. B., De Jager, P. L., Seyfried, N. T., Liu, Z., et al. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00405-4 · Cited by 75 · see citing works
Rayaprolu, S., Gao, T., Xiao, H., Ramesha, S., Weinstock, L. D., Shah, J., Duong, D. M., Dammer, E. B., Webster, J. A., Lah, J. J., et al. (2019) · doi:10.1101/802694 · Cited by 71 · see citing works
Novel isoenzyme of 2‐oxoglutarate dehydrogenase is identified in brain, but not in heart
Bunik, V. I., Kaehne, T., Degtyarev, D., Shcherbakova, T. A., & Reiser, G. (2008) · FEBS Journal · doi:10.1111/j.1742-4658.2008.06632.x · Cited by 68 · see citing works
Savas, J. N., Wang, Y.-Z., DeNardo, L. A., Martinez-Bartolome, S., McClatchy, D. B., Hark, T. J., Shanks, N. F., Cozzolino, K. A., Lavallée-Adam, M., Smukowski, S. N., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.11.009 · Cited by 66 · see citing works
The Ezrin-Radixin-Moesin Family of Proteins in the Regulation of B-Cell Immune Response
Pore, D., & Gupta, N. (2015) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.2015012327 · Cited by 64 · see citing works
Transcriptional signatures of tau and amyloid neuropathology
Castanho, I., Murray, T. K., Hannon, E., Jeffries, A., Walker, E., Laing, E., Baulf, H., Harvey, J., Bradshaw, L., Randall, A., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.01.063 · Cited by 62 · see citing works
The Role of Mitochondrial Dysfunction in the Progression of Alzheimer’s Disease
Desler, C., Lillenes, M. S., Tønjum, T., & Rasmussen, L. J. (2017) · Current Medicinal Chemistry · doi:10.2174/0929867324666170616110111 · Cited by 61 · see citing works
Tripathy, R., Leca, I., van Dijk, T., Weiss, M. M., van Bon, B. W. M., Sergaki, M. C., Gstrein, T., Breuss, M. W., Tian, G., Bahi‐Buisson, N., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.044 · Cited by 61 · see citing works
Dougherty, R. J., Schultz, S. A., Kirby, T., Boots, E. A., Oh, J. M., Edwards, D. F., Gallagher, C. L., Carlsson, C. M., Bendlin, B. B., Asthana, S., et al. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161067 · Cited by 50 · see citing works
Phosphoproteomics identifies microglial Siglec‐F inflammatory response during neurodegeneration
Morshed, N., Ralvenius, W. T., Nott, A., Watson, L. A., Rodriguez, F. H., Akay, L. A., Joughin, B. A., Pao, P., Penney, J., LaRocque, L. M., et al. (2020) · Molecular Systems Biology · doi:10.15252/msb.20209819 · Cited by 46 · see citing works
Imai, Y., Inoshita, T., Meng, H., Shiba‐Fukushima, K., Hara, K. Y., Sawamura, N., & Hattori, N. (2019) · Communications Biology · doi:10.1038/s42003-019-0674-1 · Cited by 45 · see citing works
Microglial reaction in Pick's disease
Paulus, W., Bancher, C., & Jellinger, K. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90147-d · Cited by 42 · see citing works
Velasco, A. L., Fraser, G. M., Delobel, P., Ghetti, B. F., Lavenir, I., & Goedert, M. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.02.025 · Cited by 40 · see citing works
Takeda, K., Uda, A., Mitsubori, M., Nagashima, S., Iwasaki, H., Ito, N., Shiiba, I., Ishido, S., Matsuoka, M., Inatome, R., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-01720-2 · Cited by 32 · see citing works
Tau Pathology Induces Intraneuronal Cholesterol Accumulation
Glöckner, F., & Ohm, T. G. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000103 · Cited by 30 · see citing works
Distinct phosphorylation profiles of tau in brains of patients with different tauopathies
Samimi, N., Sharma, G., Kimura, T., Matsubara, T., Huo, A., Chiba, K., Saito, Y., Murayama, S., Akatsu, H., Hashizume, Y., et al. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2021.08.011 · Cited by 29 · see citing works
Protein kinase A mediates microglial activation induced by plasminogen and gangliosides
Min, K., Yang, M.-S., Jou, I., & Joe, E.-H. (2004) · Experimental & Molecular Medicine · doi:10.1038/emm.2004.58 · Cited by 27 · see citing works
Proteomic profiling of brain cortex tissues in a Tau transgenic mouse model of Alzheimer’s disease
Chang, S.-H., Jung, I.-S., Han, G.-Y., Kim, N., Kim, H.-J., & Kim, C. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.11.093 · Cited by 27 · see citing works
Wang, C., Zhao, F., Shen, K., Wang, W., Siedlak, S. L., Lee, H., Phelix, C. F., Perry, G., Shen, L., Tang, B., et al. (2019) · Brain Pathology · doi:10.1111/bpa.12691 · Cited by 18 · see citing works
Motif-centric phosphoproteomics to target kinase-mediated signaling pathways
Tsai, C., Ogata, K., Sugiyama, N., & Ishihama, Y. (2022) · Cell Reports Methods · doi:10.1016/j.crmeth.2021.100138 · Cited by 18 · see citing works
Epitope Fingerprinting for Recognition of the Polyclonal Serum Autoantibodies of Alzheimer’s Disease
Júnior, L. C. O., Santos, F. D. A. A., Goulart, L. R., & Ueira‐Vieira, C. (2015) · BioMed Research International · doi:10.1155/2015/267989 · Cited by 10 · see citing works
Pathogenic tau disrupts the cellular program that maintains neuronal identityPreprint
Beckmann, A., Ramirez, P., Gamez, M., Ray, W. J., & Frost, B. E. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.03.05.434166 · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Ren, F., Wei, J., Chen, Q., Hu, M., Yu, L., Mi, J., Zhou, X., Qin, D., Wu, J., & Wu, A. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.07.030 · Cited by 97 · see citing works
Toral-Ríos, D., Long, J. M., Ulrich, J. D., Yu, J., Strickland, M. R., Han, X., Holtzman, D. M., Cashikar, A. G., & Paul, S. M. (2024) · The Journal of Experimental Medicine · doi:10.1084/jem.20232000 · Cited by 47 · see citing works
Sharp, F. R., DeCarli, C. S., Jin, L., & Zhan, X. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1096206 · Cited by 30 · see citing works
Collu, R., Yin, Z., Giunti, E., Daley, S. A., Chen, M., Morin, P., Killick, R., Wong, S. T. C., & Xia, W. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1323563 · Cited by 20 · see citing works
Tau–Mitochondria Interactions in Neurodegeneration: Mechanisms and Therapeutic Potential
Castillo-Casaña, Y., Arias, C., & Coria, R. (2025) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-025-01634-1 · Cited by 15 · see citing works
Yu, F., Iacono, D., Perl, D. P., Lai, C., Gill, J., Le, T. Q., Lee, P. J., Sukumar, G., & Armstrong, R. C. (2023) · Acta Neuropathologica · doi:10.1007/s00401-023-02622-9 · Cited by 15 · see citing works
Tsumagari, K., Sato, Y., Aoyagi, H., Okano, H., & Kuromitsu, J. (2023) · Scientific Reports · doi:10.1038/s41598-023-45570-w · Cited by 14 · see citing works
Self-citationMolecular landscape of the overlap between Alzheimer’s disease and somatic insulin-related diseases
Ruisch, I. H., Widomska, J., Witte, W. D., Mota, N. R., Fanelli, G., van Gils, V., Jansen, W. J., Vos, S. J. B., Fóthi, Á., Barta, C., et al. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01609-2 · Cited by 10 · see citing works
Silvestre, D. D., Brambilla, F., Lavatelli, F., Chirivì, M., Canetti, D., Bearzi, C., Rizzi, R., Bijzet, J., Hazenberg, B. P. C., Bellotti, V., et al. (2023) · Cells · doi:10.3390/cells12050699 · Cited by 10 · see citing works
CoPPIs algorithm: a tool to unravel protein cooperative strategies in pathophysiological conditions
Lomagno, A., Yusuf, I., Tosadori, G., Bonanomi, D., Mauri, P. L., & Silvestre, D. D. (2025) · Briefings in Bioinformatics · doi:10.1093/bib/bbaf146 · Cited by 4 · see citing works
Juanes, A. M., Vogels, T., Hertog, S. K.-D., Loos, M., Lütjohann, D., Giera, M. A., & van der Kant, R. (2025) · Journal of Lipid Research · doi:10.1016/j.jlr.2025.100952 · Cited by 3 · see citing works
HIV-2 mediated effects on target and bystander cells induce plasma proteome remodeling
Johansson, E., Nazziwa, J., Freyhult, E., Hong, M., Lindman, J. L., Neptin, M., Karlson, S., Rezeli, M., Biague, A. J., Medstrand, P., et al. (2024) · iScience · doi:10.1016/j.isci.2024.109344 · Cited by 1 · see citing works
Toral-Ríos, D., Long, J. M., Ulrich, J. D., Yu, J., Strickland, M. R., Han, X., Holtzman, D. M., Cashikar, A. G., & Paul, S. M. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.08.556884
Tsumagari, K., Ishihama, Y., & Imami, K. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.20.706508
Self-citationZadrożny, M., Zadrożna, P., Niewiadomski, W., Riedel, G., Harrington, C. R., Wischik, C. M., Niewiadomska, G., & Gąsiorowska, A. (2026) · Cells · doi:10.3390/cells15201908
- Authors
- Tsumagari, K., Sato, Y., Shimozawa, A., Aoyagi, H., Okano, H., & Kuromitsu, J.
- Affiliations
- Keio University (JP)
- Eisai (Japan) (JP)
- Corresponding author
- Tsumagari, Kazuya
- Kuromitsu, Junro
- Venue
- iScience
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 25
- Issue
- 8
- Pages
- 104832
- ISSN
- 2589-0042 (ISSN-L)
- PMC
- PMC9382322
- OpenAlex
- W4289857136
- Cited by
- 15
- References
- 87
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 5
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- iScience (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- RIKEN
- Japan Agency for Medical Research and Development (JP17pc0101006)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- tau protein, tau aggregates, Alzheimer's disease, neuroinflammation, mitochondrial bioenergetics, TCA cycle, oxidative phosphorylation, cholesterol biosynthesis, postsynaptic density, protein phosphorylation, proteomic profiling
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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