The DOI matches its Crossref record; 259 of the 265 references it cites were found in a registry or an index.
Microglia: Friend and foe in tauopathy
Open accessAbstract
Aggregation of misfolded microtubule associated protein tau into abnormal intracellular inclusions defines a class of neurodegenerative diseases known as tauopathies. The consistent spatiotemporal progression of tau pathology in Alzheimer's disease (AD) led to the hypothesis that tau aggregates spread in the brain via bioactive tau "seeds" underlying advancing disease course. Recent studies implicate microglia, the resident immune cells of the central nervous system, in both negative and positive regulation of tau pathology. Polymorphisms in genes that alter microglial function are associated with the development of AD and other tauopathies. Experimental manipulation of microglia function can alter tau pathology and microglia-mediated neuroinflammatory cascades can exacerbate tau pathology. Microglia also exert protective functions by mitigating tau spread: microglia internalize tau seeds and have the capacity to degrade them. However, when microglia fail to degrade these tau seeds there are deleterious consequences, including secretion of exosomes containing tau that can spread to neurons. This review explores the intersection of microglia and tau from the perspective of neuropathology, neuroimaging, genetics, transcriptomics, and molecular biology. As tau-targeted therapies such as anti-tau antibodies advance through clinical trials, it is critical to understand the interaction between tau and microglia.
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“The phagocytic activity of microglia is crucial for the removal of Aβ,94 tau,95 and α-synuclein.96”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [95]
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Items 201–259 of 259
Loss of tau rescues inflammation-mediated neurodegeneration
Maphis, N., Xu, G., Kokiko-Cochran, O. N., Cardona, A. E., Ransohoff, R. M., Lamb, B. T., & Bhaskar, K. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00196 · Cited by 91
SH3 domain‐dependent interactions of endophilin with amphiphysin
(1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01016-8 · Cited by 91
Microglia display modest phagocytic capacity for extracellular tau oligomers
Majerova, P., Zilkova, M., Kazmerova, Z., Kovac, A., Paholikova, K., Kovacech, B., Zilka, N., & Novak, M. (2014) · Journal of Neuroinflammation · doi:10.1186/s12974-014-0161-z · Cited by 90
LRRK2 and Rab10 coordinate macropinocytosis to mediate immunological responses in phagocytes
Liu, Z., Xu, E., Zhao, H. T., Cole, T., & West, A. B. (2020) · The EMBO Journal · doi:10.15252/embj.2020104862 · Cited by 90
Fox, L. M., William, C. M., Adamowicz, D. H., Pitstick, R., Carlson, G. A., Spires-Jones, T. L., & Hyman, B. T. (2011) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318220a658 · Cited by 88
Tau Aggregates: Toxic, Inert, or Protective Species?
Bretteville, A., & Planel, E. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-14411 · Cited by 87
Lee, M., McGeer, E. G., & McGeer, P. L. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.07.024 · Cited by 85
Wang, H., Li, Y., Ryder, J. W., Hole, J. T., Ebert, P. J., Airey, D. C., Qian, H.-R., Logsdon, B., Fisher, A., Ahmed, Z., et al. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0296-y · Cited by 83
Differential kinase requirements in human and mouse Fc-gamma receptor phagocytosis and endocytosis
Huang, Z.-Y., Barreda, D. R., Worth, R. G., Indik, Z. K., Kim, M.-K., Chien, P., & Schreiber, A. D. (2006) · Journal of Leukocyte Biology · doi:10.1189/jlb.0106019 · Cited by 80
Zhan, L., Fan, L., Kodama, L., Sohn, P., Wong, M. Y., Mousa, G. A., Zhou, Y., Li, Y., & Gan, L. (2020) · eLife · doi:10.7554/elife.51796 · Cited by 80
Andersson, C. R., Falsig, J., Stavenhagen, J. B., Christensen, S., Kartberg, F., Rosenqvist, N., Finsen, B. R., & Pedersen, J. T. (2019) · Scientific Reports · doi:10.1038/s41598-019-41105-4 · Cited by 79
Selective targeting of microglia by quantum dots
Minami, S., Sun, B., Popat, K. C., Kauppinen, T. M., Pleiss, M., Zhou, Y., Ward, M. E., Floreancig, P. E., Mucke, L., Desai, T. A., et al. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-22 · Cited by 79
Neniškytė, U., & Brown, G. C. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12288 · Cited by 78
Involvement of Oligodendrocytes in Tau Seeding and Spreading in Tauopathies
Ferrer, I., Aguiló, M., Carmona, M., Andrés‐Benito, P., Torrejón-Escribano, B., Garcia‐Esparcia, P., & del Rı́o, J. A. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00112 · Cited by 78
Doodnauth, S. A., Grinstein, S., & Maxson, M. E. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2018.0147 · Cited by 78
Emerging roles of microglial cathepsins in neurodegenerative disease
Lowry, J. R., & Klegeris, A. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2018.02.014 · Cited by 77
van Olst, L., Verhaege, D., Franssen, M., Kamermans, A., Roucourt, B., Carmans, S., Ytebrouck, E., van der Pol, S. M. A., Wever, D. D., Popovic, M. A., et al. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.01.003 · Cited by 76
Gerson, J. E., Castillo‐Carranza, D. L., & Kayed, R. (2014) · ACS Chemical Neuroscience · doi:10.1021/cn500143n · Cited by 75
LRP1 expression in microglia is protective during CNS autoimmunity
Chuang, T.-Y., Guo, Y. X., Seki, S. M., Rosen, A. M., Johanson, D. M., Mandell, J. W., Lucchinetti, C. F., & Gaultier, A. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0343-2 · Cited by 74
In vivo evidence for microglial activation in neurodegenerative dementia
Cagnin, A., Kassiou, M., Meikle, S. R., & Banati, R. B. (2006) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.2006.00694.x · Cited by 71
Gey, G. O., Shapras, P., & Borysko, E. (1954) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1954.tb45895.x · Cited by 71
Plaque complement activation and cognitive loss in Alzheimer's disease
Loeffler, D. A., Camp, D. M., & Bennett, D. A. (2008) · Journal of Neuroinflammation · doi:10.1186/1742-2094-5-9 · Cited by 68
Cognitive impairment in progressive supranuclear palsy is associated with tau burden
Koga, S., Parks, A. C., Kasanuki, K., Sánchez-Contreras, M., Baker, M., Josephs, K. A., Ahlskog, J. E., Uitti, R. J., Graff‐Radford, N. R., van Gerpen, J. A., et al. (2017) · Movement Disorders · doi:10.1002/mds.27198 · Cited by 67
Formation, release, and internalization of stable tau oligomers in cells
Wegmann, S., Nicholls, S. B., Takeda, S., Fan, Z., & Hyman, B. T. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13866 · Cited by 66
Extracellular tau induces microglial phagocytosis of living neurons in cell cultures
Pampuščenko, K., Morkūnienė, R., Šneideris, T., Smirnovas, V., Budvytytė, R., Valinčius, G., Brown, G. C., & Borutaitė, V. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14940 · Cited by 64
Physiological clearance of tau in the periphery and its therapeutic potential for tauopathies
Wang, J., Jin, W., Bu, X., Zeng, F., Huang, Z., Li, W., Shen, L., Zhuang, Z., Fang, Y., Sun, B., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1891-2 · Cited by 62
Das, R. R., & Chinnathambi, S. (2021) · Traffic · doi:10.1111/tra.12784 · Cited by 62
Actin dynamics shape microglia effector functions.
Uhlemann, R., Gertz, K., Boehmerle, W., Schwarz, T., Nolte, C., Freyer, D., Kettenmann, H., Endres, M., & Kronenberg, G. (2016) · Brain Structure and Function · doi:10.1007/s00429-015-1067-y · Cited by 61
Wittrup, A., Zhang, S., ten Dam, G. B., Kuppevelt, T. H. V., Bengtson, P., Johansson, M. C., Welch, J. E., Mörgelin, M., & Belting, M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.036129 · Cited by 61
Gabbita, S. P., Johnson, M. F., Kobritz, N., Eslami, P., Poteshkina, A., Varadarajan, S., Turman, J., Zemlan, F. P., & Harris‐White, M. E. (2015) · PLoS ONE · doi:10.1371/journal.pone.0137305 · Cited by 59
Redka, D. S., Gütschow, M., Grinstein, S., & Canton, J. (2018) · Molecular Biology of the Cell · doi:10.1091/mbc.e17-06-0419 · Cited by 58
Chemokine Decoy Receptors: Structure–Function and Biological Properties
Bonecchi, R., Savino, B., Borroni, E. M., Mantovani, A., & Locati, M. (2010) · Current topics in microbiology and immunology · doi:10.1007/82_2010_19 · Cited by 58
TDP-43: From Alzheimer’s Disease to Limbic-Predominant Age-Related TDP-43 Encephalopathy
Huang, W., Zhou, Y., Tu, L., Ba, Z., Huang, J., Huang, N., & Luo, Y. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00026 · Cited by 57
A Tale of Two Genes: Microglial Apoe and Trem2
Pimenova, A. A., Marcora, E. M., & Goate, A. (2017) · Immunity · doi:10.1016/j.immuni.2017.08.015 · Cited by 52
Cathepsin B: Basis Sequence: Mouse.
Cavallo‐Medved, D., Moin, K., & Sloane, B. F. (2011) · PubMed · Cited by 51
Direct interaction between CD91 and C1q
Duus, K., Hansen, E. W., Tacnet‐Delorme, P., Frachet, P., Arlaud, G. J., Thielens, N. M., & Houen, G. (2010) · FEBS Journal · doi:10.1111/j.1742-4658.2010.07762.x · Cited by 50
Odawara, T., Iseki, E., Kosaka, K., Akiyama, H., Ikeda, K., & Yamamoto, T. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)11595-n · Cited by 47
Knockin’ on heaven’s door: Molecular mechanisms of neuronal tau uptake
La‐Rocque, S. D., Moretto, E., Butnaru, I., & Schiavo, G. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15144 · Cited by 46
Tau epitope display in progressive supranuclear palsy and corticobasal degeneration
Berry, R. W., Sweet, A. P., Clark, F., Lagalwar, S., Lapin, B. R., Wang, T., Topgi, S., Guillozet-Bongaarts, A. L., Cochran, E., Bigio, E. H., et al. (2004) · Journal of Neurocytology · doi:10.1023/b:neur.0000044190.96426.b9 · Cited by 43
α-Linolenic acid induces clearance of Tau seeds via Actin-remodeling in Microglia
Desale, S. E., & Chinnathambi, S. (2021) · Molecular Biomedicine · doi:10.1186/s43556-021-00028-1 · Cited by 43
Antigenic expression of cathepsin B in aged human brain
Bernstein, H., Kirschke, H., Wiederanders, B., Schmidt, D., & Rinne, A. (1990) · Brain Research Bulletin · doi:10.1016/0361-9230(90)90157-u · Cited by 43
Evidence for motility and pinocytosis in ramified microglia in tissue culture
Booth, P. L., & Thomas, W. E. (1991) · Brain Research · doi:10.1016/0006-8993(91)91118-k · Cited by 42
Oberstein, T. J., Utz, J., Spitzer, P., Klafki, H., Wiltfang, J., Lewczuk, P., Kornhuber, J., & Maler, J. M. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.615740 · Cited by 40
Microglial tau undergoes phosphorylation‐independent modification after ischemia
Uchihara, T., Nakamura, A., Arai, T., Ikeda, K., & Tsuchiya, K. (2003) · Glia · doi:10.1002/glia.10318 · Cited by 37
Humanized tau antibodies promote tau uptake by human microglia without any increase of inflammation
Žilková, M., Nölle, A., Kováčech, B., Kontseková, E., Weisová, P., Filipčík, P., Škrabana, R., Prčina, M., Hromádka, T., Cehlár, O., et al. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-00948-z · Cited by 35
Proteolysis of Microtubule‐Associated Protein 2 and Tubulin by Cathepsin D
Johnson, G. V. W., Litersky, J. M., & Whitaker, J. N. (1991) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1991.tb06354.x · Cited by 34
Farizatto, K. L. G., Ikonne, U. S., de Almeida, M. F., Ferrari, M., & Bahr, B. A. (2017) · PLoS ONE · doi:10.1371/journal.pone.0182895 · Cited by 33
Schlegel, K., Awwad, K., Heym, R. G., Holzinger, D., Doell, A., Barghorn, S., Jahn, T. R., Klein, C., Mordashova, Y., Schulz, M., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0831-2 · Cited by 30
Macropinocytosis contributes to the macrophage foam cell formation in RAW264.7 cells
Yao, W., Li, K., & Liao, K. (2009) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmp066 · Cited by 30
Rodríguez-Callejas, J. D., Fuchs, E., & Perez‐Cruz, C. (2020) · Glia · doi:10.1002/glia.23804 · Cited by 28
Asparagine endopeptidase cleaves tau at N167 after uptake into microglia
Behrendt, A., Bichmann, M., Ercan-Herbst, E., Haberkant, P., Schöndorf, D. C., Wolf, M., Fahim, S. A., Murolo, E., & Ehrnhoefer, D. E. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104518 · Cited by 26
Appearance of tau-2 immunoreactivity in glial cells in human brain with cerebral infarction
Uchihara, T., Tsuchiya, K., Nakamura, A., & Ikeda, K. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01103-4 · Cited by 24
Pinocytosis as a select marker of ramified microglia in vivo and in vitro.
Ranson, P. A., & Thomas, W. E. (1991) · Journal of Histochemistry & Cytochemistry · doi:10.1177/39.6.2033242 · Cited by 23
Nübling, G., Schuberth, M., Feldmer, K., Giese, A., Holdt, L., Teupser, D., & Lorenzl, S. (2017) · Experimental Brain Research · doi:10.1007/s00221-017-4978-4 · Cited by 23
Uchihara, T., Duyckaerts, C. J., Seilhean, D., Nakamura, A., Lazarini, F., & Hauw, J. (2004) · Acta Neuropathologica · doi:10.1007/s00401-004-0922-3 · Cited by 16
Microglial activation and tau propagate jointly across Braak stages
Pascoal, T. A., Benedet, A. L., Ashton, N. J., Kang, M. S., Therriault, J., Chamoun, M., Lussier, F. Z., Tissot, C., Ottoy, J., Mathotaarachchi, S., et al. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.056653 · Cited by 15
Ibarra-Bracamontes, V., Escobar‐Herrera, J., Krištofíková, Z., Řı́pová, D., Florán, B., & García‐Sierra, F. (2020) · Brain Research · doi:10.1016/j.brainres.2020.146953 · Cited by 14
Tau Isoform-Driven CBD Pathology Transmission in Oligodendrocytes in Humanized Tau Mice
Zarȩba-Pasławska, J., Patra, K., Kluzer, L., Révész, T., & Svenningsson, P. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2020.589471 · Cited by 14
Taylor, S., Craig, D., Qu, L., Haines, J. L., Morgan, T., Sager, M. A., Jun, G., Beiser, A., George‐Hyslop, P. S., Levey, A. I., et al. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/pbds-w495 · Cited by 2
Flagged first, then by citations
6 of the 265 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Lewis, 1931, Pinocytosis, Bull. Johns. Hopkins Hosp., 49, 17
- Wang, P., Ye, Y., 2020. An integrin receptor complex mediates filamentous Tau-induced activation of primary astrocytes. bioRxiv 2020.05.07.083295. https://doi.org/10.1101/2020.05.07.083295. · DOI
Cited by
Sorted by citations
Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193
Neuroinflammation across neurological diseases
Shi, F., & Yong, V. W. (2025) · Science · doi:10.1126/science.adx0043 · Cited by 325
Quick, J. D., Silva, C., Wong, J. H., Lim, K. L., Reynolds, R., Barron, A. M., Zeng, J., & Lo, C. H. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02866-y · Cited by 203
“Bidirectional relationship between toxic protein aggregates and lysosomal dysfunction The accumulation of toxic protein aggregates such as tau and Aβ is associated with neurodegeneration [81–86] and microglia have been shown to play an important role in the internalization and degradation of these toxic protein aggreg…”
BackgroundTau in neurodegenerative diseases: molecular mechanisms, biomarkers, and therapeutic strategies
Zhang, X., Wang, J., Zhang, Z., & Ye, K. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00429-6 · Cited by 119
“Multiple mechanisms are involved in tau uptake by microglia, including phagocytosis, macropinocytosis, and micropinocytosis [139].”
BackgroundThe Yin and Yang of Microglia-Derived Extracellular Vesicles in CNS Injury and Diseases
Ghosh, M., & Pearse, D. D. (2024) · Cells · doi:10.3390/cells13221834 · Cited by 69
Metadata
- Authors
- Odfalk, K. F., Bieniek, K. F., & Hopp, S. C.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Hopp, Sarah C.
- Venue
- Progress in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2022-09
- Volume
- 216
- Pages
- 102306
- ISSN
- 0301-0082 (ISSN-L)
- PMC
- PMC9378545
- OpenAlex
- W4282841274
- Cited by
- 60
- References
- 265
- Citations by year
- 2026: 17 · 2025: 19 · 2024: 13 · 2023: 8 · 2022: 3
- FWCI
- 1.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 480 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Progress in Neurobiology (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (K01AG066747, R21AG072423, R01AG062348, R01AG070214, P30AG066546)
- National Institute of Neurological Disorders and Stroke (T32NS082145, R01NS017950)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- microglia, tauopathy, tau aggregation, Alzheimer's disease, tau seeding, neuroinflammation, tau spread, exosomes, anti-tau antibodies, tau-targeted therapy
- MeSH terms
- Alzheimer Disease, Brain, Humans, Neurons, tau Proteins, Microglia, Tauopathies
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