Intersection of pathological tau and microglia at the synapse

Vogels, Thomas; Murgoci, Adriana-Natalia; Hromádka, Tomáš

doi:10.1186/s40478-019-0754-y

Cited by 197Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsNeurological Disease Mechanisms and Treatments

Intersection of pathological tau and microglia at the synapse

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Vogels, Thomas, Murgoci, Adriana-Natalia, Hromádka, Tomáš·2019·Acta Neuropathologica Communications

DOI 10.1186/s40478-019-0754-yPMC PMC6612163

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Abstract

Tauopathies are a heterogenous class of diseases characterized by cellular accumulation of aggregated tau and include diseases such as Alzheimer's disease (AD), progressive supranuclear palsy and chronic traumatic encephalopathy. Tau pathology is strongly linked to neurodegeneration and clinical symptoms in tauopathy patients. Furthermore, synapse loss is an early pathological event in tauopathies and is the strongest correlate of cognitive decline. Tau pathology is additionally associated with chronic neuroinflammatory processes, such as reactive microglia, astrocytes, and increased levels of pro-inflammatory molecules (e.g. complement proteins, cytokines). Recent studies show that as the principal immune cells of the brain, microglia play a particularly important role in the initiation and progression of tau pathology and associated neurodegeneration. Furthermore, AD risk genes such as Triggering receptor expressed on myeloid cells 2 (TREM2) and Apolipoprotein E (APOE) are enriched in the innate immune system and modulate the neuroinflammatory response of microglia to tau pathology. Microglia can play an active role in synaptic dysfunction by abnormally phagocytosing synaptic compartments of neurons with tau pathology. Furthermore, microglia are involved in synaptic spreading of tau - a process which is thought to underlie the progressive nature of tau pathology propagation through the brain. Spreading of pathological tau is also the predominant target for tau-based immunotherapy. Active tau vaccines, therapeutic tau antibodies and other approaches targeting the immune system are actively explored as treatment options for AD and other tauopathies. This review describes the role of microglia in the pathobiology of tauopathies and the mechanism of action of potential therapeutics targeting the immune system in tauopathies.

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Microglia may contribute to tau pathology.
“it has been suggested that microglia may also contribute to tau pathology”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [328]
Microglia are implicated in pathological spreading of tau via release of extracellular vesicles.
“Microglia have also been implicated in the pathological spreading of tau via the release of extracellular vesicles [12, 61, 328]”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [328]
Microglia contribute to tau pathology, spread, and synaptic degeneration.
“It would be of interest to include microglia in the model, given their contribution to tau pathology, spread, and synaptic degeneration (Vogels et al., 2019).”
From ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids (2021) · cites this paper as Vogels et al., 2019
Multi-tracer PET studies support previous in vitro evidence of an association between microglial activation and tau aggregation in different tauopathies.
“Collectively, these multi-tracer PET studies support previous in vitro evidence of the association between microglial activation and tau aggregation in different tauopathies41.”
From Neuroinflammation and Tau Colocalize in vivo in Progressive Supranuclear Palsy (2020) · cites this paper as [41]

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Castillo-Carranza, D. L., Sengupta, U., Guerrero-Muñoz, M. J., Lasagna-Reeves, C. A., Gerson, J. E., Singh, G., Estes, D. M., Barrett, A. D. T., Dineley, K. T., Jackson, G. R., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3192-13.2014 · Cited by 278 · cited 2× · see citing works
“↓ P-tau, ↓insoluble tau, NC survival, NC micro- and astrogliosis Castillo-Carranza (2014) [53] TOMA (conformational) JPNL3 8M Single injection (30ug/mouse i.v. & 1ug/mouse i.c.v) ↓Tau oligomers, NC microgliosis and cytokines, improved cognition & motor deficits Castillo-Carranza (2014) [50] TOMA…”
Background
SIRT1 Deficiency in Microglia Contributes to Cognitive Decline in Aging and Neurodegeneration via Epigenetic Regulation of IL-1β
Cho, S.-H., Chen, J. A., Sayed, F., Ward, M. E., Gao, F., Nguyen, T. A., Krabbe, G., Sohn, P. D., Lo, I., Minami, S., et al. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2939-14.2015 · Cited by 275 · see citing works
Lost after translation: missorting of Tau protein and consequences for Alzheimer disease
Zempel, H., & Mandelkow�, E. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.08.004 · Cited by 272 · see citing works
Immunotherapy Targeting Pathological Tau Prevents Cognitive Decline in a New Tangle Mouse Model
Boutajangout, A., Quartermain, D., & Sigurdsson, E. M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4363-10.2010 · Cited by 272 · see citing works
Extracellular Vesicles Isolated from the Brains of rTg4510 Mice Seed Tau Protein Aggregation in a Threshold-dependent Manner
Polanco, J. C., Scicluna, B. J., Hill, A. F., & Götz, J. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.709485 · Cited by 271 · see citing works
Treatment with a C5aR Antagonist Decreases Pathology and Enhances Behavioral Performance in Murine Models of Alzheimer’s Disease
Fonseca, M. I., Ager, R. R., Chu, S.-H., Yazan, O., Sanderson, S. D., LaFerla, F. M., Taylor, S. M., Woodruff, T. M., & Tenner, A. J. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901005 · Cited by 268 · see citing works
Microglial neuroinflammation contributes to tau accumulation in chronic traumatic encephalopathy
Cherry, J. D., Tripodis, Y., Alvarez, V. E., Huber, B., Kiernan, P. T., Daneshvar, D., Mez, J., Montenigro, P., Solomon, T. M., Alosco, M., et al. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0382-8 · Cited by 267 · see citing works
Loss of Bin1 Promotes the Propagation of Tau Pathology
Calafate, S., Flavin, W., Verstreken, P., & Moechars, D. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.09.063 · Cited by 265 · see citing works
Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau
Kang, S. S., Ebbert, M. T. W., Baker, K. E., Cook, C., Wang, X., Sens, J. P., Kocher, J.-P., Petrucelli, L., & Fryer, J. D. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20180653 · Cited by 260 · see citing works
Efficacy and Safety of A Liposome-Based Vaccine against Protein Tau, Assessed in Tau.P301L Mice That Model Tauopathy
Theunis, C., Crespo-Biel, N., Gafner, V., Pihlgren, M., López-Deber, M. P., Reis, P., Hickman, D. T., Adolfsson, O., Chuard, N., Ndao, D. M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072301 · Cited by 259 · see citing works
Tau seeding activity begins in the transentorhinal/entorhinal regions and anticipates phospho-tau pathology in Alzheimer’s disease and PART
Kaufman, S. K., Del Tredici, K., Thomas, T. L., Braak, H., & Diamond, M. I. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1855-6 · Cited by 259 · see citing works
Molecular and Cellular Characterization of the Membrane Attack Complex, C5b-9, in Alzheimer’s Disease
Webster, S. D., Lue, L., Brachova, L., Tenner, A. J., McGeer, P. L., Terai, K., Walker, D. G., Bradt, B. M., Cooper, N. R., & Rogers, J. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00042-0 · Cited by 258 · see citing works
Disease-related microglia heterogeneity in the hippocampus of Alzheimer’s disease, dementia with Lewy bodies, and hippocampal sclerosis of aging
Bachstetter, A. D., Van Eldik, L. J., Schmitt, F. A., Neltner, J. H., Ighodaro, E. T., Webster, S. J., Patel, E., Abner, E. L., Kryscio, R. J., & Nelson, P. T. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0209-z · Cited by 258 · see citing works
Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation
Calafate, S., Buist, A., Miśkiewicz, K., Vijayan, V. A., Daneels, G., Strooper, B. D., de Wit, J., Verstreken, P., & Moechars, D. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.043 · Cited by 257 · see citing works
Truncated tau from sporadic Alzheimer's disease suffices to drive neurofibrillary degeneration in vivo
Žilka, N., Filipčík, P., Koson, P., Fialová, Ľ., Škrabana, R., Žilková, M., Rolkova, G., Kontseková, E., & Novák, M. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.05.029 · Cited by 254 · see citing works
Ferritin is a component of the neuritic (senile) plaque in Alzheimer dementia
Grundke, I., Fleming, J. T., Tung, Y. C., Lassmann, H., Iqbal, K., & Joshi, J. G. (1990) · Acta Neuropathologica · doi:10.1007/bf00334497 · Cited by 253 · see citing works
TFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading
Martini-Stoica, H., Cole, A. L., Swartzlander, D. B., Chen, F., Wan, Y.-W., Bajaj, L., Bader, D. A., Lee, V. M. Y., Trojanowski, J. Q., Liu, Z., et al. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20172158 · Cited by 253 · see citing works
Conformation Determines the Seeding Potencies of Native and Recombinant Tau Aggregates
Falcon, B., Cavallini, A., Angers, R. C., Glover, S. J., Murray, T. K., Barnham, L., Jackson, S., O'Neill, M. J., Isaacs, A. M., Hutton, M. L., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.589309 · Cited by 252 · see citing works
Unconventional Secretion Mediates the Trans-cellular Spreading of Tau
Katsinelos, T., Zeitler, M., Dimou, E., Karakatsani, A., Müller, H., Nachman, E., Steringer, J. P., de Almodóvar, C. R., Nickel, W., & Jahn, T. R. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.056 · Cited by 252 · see citing works
Microglia show altered morphology and reduced arborization in human brain during aging and <scp>A</scp>lzheimer's disease
Davies, D. S., Ma, J., Jegathees, T., & Goldsbury, C. (2017) · Brain Pathology · doi:10.1111/bpa.12456 · Cited by 251 · see citing works
Identification of the Tau phosphorylation pattern that drives its aggregation
Despres, C., Byrne, C., Qi, H., Cantrelle, F., Huvent, I., Chambraud, B., Baulieu, É.-É., Jacquot, Y., Landrieu, I., Lippens, G. M., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1708448114 · Cited by 246 · see citing works
Microglial TNF-α Suppresses Cocaine-Induced Plasticity and Behavioral Sensitization
Lewitus, G. M., Konefal, S., Greenhalgh, A. D., Pribiag, H., Augereau, K., & Stellwagen, D. (2016) · Neuron · doi:10.1016/j.neuron.2016.03.030 · Cited by 244 · see citing works
Microglia in Alzheimer's Disease: Exploring How Genetics and Phenotype Influence Risk
McQuade, A., & Blurton-Jones, M. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.01.045 · Cited by 244 · see citing works
Requirement for Microglia for the Maintenance of Synaptic Function and Integrity in the Mature Retina
Wang, X., Zhao, L., Zhang, J., Fariss, R. N., Ma, W., Kretschmer, F., Wang, M., Qian, H., Badea, T. C., Diamond, J. S., et al. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.3575-15.2016 · Cited by 242 · see citing works
Novel allele-dependent role for APOE in controlling the rate of synapse pruning by astrocytes
Chung, W.-S., Verghese, P. B., Chakraborty, C., Joung, J., Hyman, B. T., Ulrich, J. D., Holtzman, D. M., & Barres, B. A. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1609896113 · Cited by 242 · see citing works
Microglial internalization and degradation of pathological tau is enhanced by an anti-tau monoclonal antibody
Luo, W., Liu, W., Hu, X., Hanna, M., Caravaca, A., & Paul, S. M. (2015) · Scientific Reports · doi:10.1038/srep11161 · Cited by 241 · see citing works
Direct Evidence of Internalization of Tau by Microglia In Vitro and In Vivo
Bolós, M., Llorens-Martín, M., Jurado-Arjona, J., Hernández, F., Rábano, A., & Avila, J. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-150704 · Cited by 234 · 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
Differential effects of partial and complete loss of TREM2 on microglial injury response and tauopathy
Sayed, F. A., Telpoukhovskaia, M., Kodama, L., Li, Y., Zhou, Y., Le, D., Hauduc, A., Ludwig, C., Gao, F., Clelland, C., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1811411115 · Cited by 229 · cited 2× · see citing works
“Indeed, haploinsufficiency of AD risk gene TREM2 only leads to impaired response of microglia to injury in old mice [261].”
Background
The roles of inflammation and immune mechanisms in Alzheimer's disease
Eldik, L. J. V., Carrillo, M. C., Cole, P. E., Feuerbach, D., Greenberg, B., Hendrix, J. A., Kennedy, M. E., Kozauer, N., Margolin, R. A., Molinuevo, J. L., et al. (2016) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2016.05.001 · Cited by 226 · see citing works
Inert and seed-competent tau monomers suggest structural origins of aggregation
Mirbaha, H., Chen, D., Morazova, O. A., Ruff, K. M., Sharma, A. M., Liu, X., Goodarzi, M., Pappu, R. V., Colby, D. W., Mirzaei, H., et al. (2018) · eLife · doi:10.7554/elife.36584 · Cited by 225 · see citing works
Localization and Cell Association of C1q in Alzheimer's Disease Brain
Afagh, A., Cummings, B. J., Cribbs, D. H., Cotman, C. W., & Tenner, A. J. (1996) · Experimental Neurology · doi:10.1006/exnr.1996.0043 · Cited by 224 · see citing works
Chronic Neuron-Specific Tumor Necrosis Factor-Alpha Expression Enhances the Local Inflammatory Environment Ultimately Leading to Neuronal Death in 3xTg-AD Mice
Janelsins, M. C., Mastrangelo, M. A., Park, K. M., Sudol, K. L., Narrow, W. C., Oddo, S., LaFerla, F. M., Callahan, L. M., Federoff, H. J., & Bowers, W. J. (2008) · The American Journal of Pathology · doi:10.2353/ajpath.2008.080528 · Cited by 220 · see citing works
Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease
Gomez‐Arboledas, A., Davila, J. C., Sanchez‐Mejias, E., Navarro, V., Nuñez‐Diaz, C., Sanchez‐Varo, R., Sanchez‐Mico, M. V., Trujillo‐Estrada, L., Fernandez‐Valenzuela, J. J., Vizuete, M., et al. (2018) · Glia · doi:10.1002/glia.23270 · Cited by 220 · see citing works
Ectosomes: A New Mechanism for Non-Exosomal Secretion of Tau Protein
Dujardin, S., Bégard, S., Caillierez, R., Lachaud, C., Delattre, L., Carrier, S., Loyens, A., Galas, M., Bousset, L., Melki, R., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0100760 · Cited by 215 · see citing works
Glial-Neuronal Interactions in Alzheimer Disease
Sheng, J. G., Mrak, R. E., & Griffin, W. S. T. (1997) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199703000-00007 · Cited by 215 · see citing works
Dural lymphatics regulate clearance of extracellular tau from the CNS
Patel, T. K., Habimana-Griffin, L., Gao, X., Xu, B. J., Achilefu, S., Alitalo, K. K., McKee, C. A., Sheehan, P. W., Musiek, E. S., Xiong, C., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0312-x · Cited by 215 · see citing works
Tau Internalization is Regulated by 6-O Sulfation on Heparan Sulfate Proteoglycans (HSPGs)
Rauch, J. N., Chen, J. J., Sorum, A. W., Miller, G. M., Sharf, T., See, S. K., Hsieh-Wilson, L. C., Kampmann, M., & Kosik, K. S. (2018) · Scientific Reports · doi:10.1038/s41598-018-24904-z · Cited by 211 · see citing works
Inflammation Induced by Infection Potentiates Tau Pathological Features in Transgenic Mice
Sy, M., Kitazawa, M., Medeiros, R., Whitman, L., Cheng, D., Lane, T. E., & LaFerla, F. M. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.02.012 · Cited by 210 · see citing works
A somatic mutation in erythro-myeloid progenitors causes neurodegenerative disease
Mass, E., Jacome-Galarza, C. E., Blank, T., Lazarov, T., Durham, B. H., Ozkaya, N., Pastore, A., Schwabenland, M., Chung, Y. R., Rosenblum, M. K., et al. (2017) · Nature · doi:10.1038/nature23672 · Cited by 210 · see citing works
Microglial Activation parallels System Degeneration in progressive Supranuclear palsy and Corticobasal Degeneration
Ishizawa, K., & Dickson, D. W. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.6.647 · Cited by 209 · see citing works
Atypical, non-standard functions of the microtubule associated Tau protein
Sotiropoulos, I., Galas, M., Silva, J. M., Skoulakis, E. M. C., Wegmann, S., Maina, M. B., Blum, D. L., Sayas, C. L., Mandelkow, E., Mandelkow�, E., et al. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0489-6 · Cited by 207 · see citing works
Tunneling nanotubes: A possible highway in the spreading of tau and other prion-like proteins in neurodegenerative diseases
Abounit, S., Wu, J. W., Duff, K., Victoria, G. S., & Zurzolo, C. (2016) · Prion · doi:10.1080/19336896.2016.1223003 · Cited by 206 · see citing works
Microglia Enhance Synapse Activity to Promote Local Network Synchronization
Akiyoshi, R., Wake, H., Kato, D., Horiuchi, H., Ono, R., Ikegami, A., Haruwaka, K., Omori, T., Tachibana, Y., Moorhouse, A. J., et al. (2018) · eNeuro · doi:10.1523/eneuro.0088-18.2018 · Cited by 203 · see citing works
Transgenic Mouse Model of Tau Pathology in Astrocytes Leading to Nervous System Degeneration
Forman, M. S., Lal, D., Zhang, B., Dabir, D. V., Swanson, E., Lee, V. M.-Y., & Trojanowski, J. Q. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.0081-05.2005 · Cited by 198 · see citing works
Living Neurons with Tau Filaments Aberrantly Expose Phosphatidylserine and Are Phagocytosed by Microglia
Brelstaff, J., Tolkovsky, A. M., Ghetti, B., Goedert, M., & Spillantini, M. G. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.07.072 · Cited by 195 · see citing works
Tau depletion prevents progressive blood-brain barrier damage in a mouse model of tauopathy
Blair, L. J., Frauen, H. D., Zhang, B., Nordhues, B. A., Bijan, S., Lin, Y.-C., Zamudio, F., Hernandez, L. D., Sabbagh, J. J., Selenica, M.-L. B., et al. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0186-2 · Cited by 193 · see citing works
Temporal Accrual of Complement Proteins in Amyloid Plaques in Down's Syndrome with Alzheimer's Disease
Stoltzner, S. E., Grenfell, T. J., Mori, C., Wisniewski, K. E., Wisniewski, T. M., Selkoe, D. J., & Lemere, C. A. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64753-0 · Cited by 187 · see citing works
Combined effects of scanning ultrasound and a tau-specific single chain antibody in a tau transgenic mouse model
Nisbet, R. M., Van der Jeugd, A., Leinenga, G., Evans, H. T., Janowicz, P. W., & Götz, J. (2017) · Brain · doi:10.1093/brain/awx052 · Cited by 187 · cited 1× · see citing works
“Indeed, peripheral or AAVmediated delivery of tau scFv (without an Fc domain) seems to be an effective therapeutic approach in tauopathy mice [145, 224, 283, 306].”
Extracellular Monomeric and Aggregated Tau Efficiently Enter Human Neurons through Overlapping but Distinct Pathways
Evans, L., Wassmer, T., Fraser, G. M., Smith, J. C., Perkinton, M. S., Billinton, A., & Livesey, F. J. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.021 · Cited by 187 · see citing works
Tau passive immunization inhibits not only tau but also Aβ pathology
Dai, C., Tung, Y. C., Liu, F., Gong, C., & Iqbal, K. (2017) · Alzheimer s Research & Therapy · doi:10.1186/s13195-016-0227-5 · Cited by 186 · see citing works
Local apoptotic-like mechanisms underlie complement-mediated synaptic pruning
Györffy, B. A., Kun, J., Török, G., Bulyáki, É., Borhegyi, Z., Gulyássy, P., Kis, V., Szocsics, P., Micsonai, A., Matkó, J., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1722613115 · Cited by 186 · see citing works
Complement activation by neurofibrillary tangles in Alzheimer's disease
Shen, Y., Lue, L.-F., Yang, L.-B., Roher, A., Kuo, Y.-M., Strohmeyer, R., Goux, W. J., Lee, V., Johnson, G. V. W., Webster, S. D., et al. (2001) · Neuroscience Letters · doi:10.1016/s0304-3940(01)01842-0 · Cited by 185 · see citing works
Anti‐tau antibody reduces insoluble tau and decreases brain atrophy
Yanamandra, K., Jiang, H., Mahan, T. E., Maloney, S. E., Wozniak, D. F., Diamond, M. I., & Holtzman, D. M. (2015) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.176 · Cited by 185 · see citing works
Specific Targeting of Tau Oligomers in Htau Mice Prevents Cognitive Impairment and Tau Toxicity Following Injection with Brain-Derived Tau Oligomeric Seeds
Castillo‐Carranza, D. L., Gerson, J. E., Sengupta, U., Guerrero‐Munoz, M. J., Lasagna‐Reeves, C. A., & Kayed, R. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-132477 · Cited by 180 · see citing works
Specific glycosaminoglycan chain length and sulfation patterns are required for cell uptake of tau versus α-synuclein and β-amyloid aggregates
Stopschinski, B. E., Holmes, B. B., Miller, G. M., Manon, V. A., Vaquer-Alicea, J., Prueitt, W. L., Hsieh-Wilson, L. C., & Diamond, M. I. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.000378 · Cited by 180 · see citing works
Tauopathy-like Abnormalities and Neurologic Deficits in Mice Immunized With Neuronal Tau Protein
Rosenmann, H., Grigoriadis, N., Karussis, D., Boimel, M., Touloumi, O., Ovadia, H., & Abramsky, O. (2006) · Archives of Neurology · doi:10.1001/archneur.63.10.1459 · Cited by 178 · see citing works

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[281]Socodato R, Portugal CC, Canedo T, Henriques J, Vaz SH, Magalhaes JD, Silva CM, Baptista FI, Alves RL, Nogueira J, Coelho-Santos V, Silva AP, Paes-de-Carvalho R, Magalhaes A, Summavielle T, Brakebusch C, Sebastiao AM, Ambrosio AF, Relvas JB (2017) Genetic ablation of RhoA in adult microglia causes synapse and neuronal loss. bioRxiv

Sorted by citations

Western diet as a trigger of Alzheimer’s disease: From metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration
Więckowska-Gacek, A., Mietelska-Porowska, A., Wydrych, M., & Wojda, U. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101397 · Cited by 343 · see citing works
Neuroprotective effect of SGLT2 inhibitors.
Pawlos, A., Broncel, M., Woźniak, E., & Gorzelak-Pabiś, P. (2021) · Molecules · doi:10.3390/molecules26237213 · Cited by 304 · see citing works
Tau: Enabler of diverse brain disorders and target of rapidly evolving therapeutic strategies
Chang, C.-W., Shao, E., & Mucke, L. (2021) · Science · doi:10.1126/science.abb8255 · Cited by 263 · see citing works
Shaping Neuronal Fate: Functional Heterogeneity of Direct Microglia-Neuron Interactions
Cserép, C., Pósfai, B., & Dénes, Á. (2021) · Neuron · doi:10.1016/j.neuron.2020.11.007 · Cited by 256 · see citing works
Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function
Spiteri, A. G., Wishart, C. L., Pamphlett, R., Locatelli, G., & King, N. J. C. (2022) · Acta Neuropathologica · doi:10.1007/s00401-021-02384-2 · Cited by 216 · see citing works
“Microglia have also been implicated in the pathological spreading of tau via the release of extracellular vesicles [12, 61, 328].”
Background
Neuroinflammation and the Kynurenine Pathway in CNS Disease: Molecular Mechanisms and Therapeutic Implications
Mithaiwala, M. N., Santana-Coelho, D., Porter, G. A., & O’Connor, J. C. (2021) · Cells · doi:10.3390/cells10061548 · Cited by 190 · see citing works
Fluid Biomarkers for Synaptic Dysfunction and Loss
Camporesi, E., Nilsson, J., Brinkmalm, A., Becker, B., Ashton, N. J., Blennow, K., & Zetterberg, H. (2020) · Biomarker Insights · doi:10.1177/1177271920950319 · Cited by 165 · see citing works
ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids
Bowles, K. R., Silva, M. C., Whitney, K., Bertucci, T., Berlind, J. E., Lai, J. D., Garza, J. C., Boles, N. C., Mahali, S., Strang, K. H., et al. (2021) · Cell · doi:10.1016/j.cell.2021.07.003 · Cited by 175 · see citing works
Blood-brain barrier leakage in Alzheimer’s disease: From discovery to clinical relevance
Nehra, G., Bauer, B., & Hartz, A. M. S. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108119 · Cited by 127 · see citing works
TREM2 ectodomain and its soluble form in Alzheimer’s disease
Yang, J., Fu, Z., Zhang, X., Xiong, M., Meng, L., & Zhang, Z. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01878-2 · Cited by 113 · see citing works
Tau Oligomer–Containing Synapse Elimination by Microglia and Astrocytes in Alzheimer Disease
Taddei, R. N., Perbet, R., Mate de Gerando, A., Wiedmer, A. E., Sanchez-Mico, M., Connors Stewart, T., Gaona, A., Melloni, A., Amaral, A. C., Duff, K., et al. (2023) · JAMA Neurology · doi:10.1001/jamaneurol.2023.3530 · Cited by 110 · see citing works
Tau fibrils induce glial inflammation and neuropathology via TLR2 in Alzheimer’s disease–related mouse models
Dutta, D., Jana, M., Paidi, R. K., Majumder, M., Raha, S., Dasarathy, S., & Pahan, K. (2023) · Journal of Clinical Investigation · doi:10.1172/jci161987 · Cited by 87 · see citing works
Neuroinflammation and Tau Colocalize in vivo in Progressive Supranuclear Palsy
Malpetti, M., Passamonti, L., Rittman, T., Jones, P. S., Vázquez Rodríguez, P., Bevan‐Jones, W. R., Hong, Y. T., Fryer, T. D., Aigbirhio, F. I., O'Brien, J. T., et al. (2020) · Annals of Neurology · doi:10.1002/ana.25911 · Cited by 83 · see citing works
Neuroinflammation predicts disease progression in progressive supranuclear palsy
Malpetti, M., Passamonti, L., Jones, P. S., Street, D., Rittman, T., Fryer, T. D., Hong, Y. T., Vàsquez Rodriguez, P., Bevan-Jones, W. R., Aigbirhio, F. I., et al. (2021) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2020-325549 · Cited by 85 · see citing works
“A growing literature supports a role for neuroinflammation in driving tau spreading and neurodegeneration in tauopathies (see Vogels et al 3 for review).”
Activated CX3CL1/Smad2 Signals Prevent Neuronal Loss and Alzheimer's Tau Pathology-Mediated Cognitive Dysfunction
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Authors: Vogels, T., Murgoci, A.-N., & Hromádka, T.
Affiliations: Slovak Academy of Sciences (SK)
Corresponding author: Hromádka, Tomáš
ORCID: Murgoci, Adriana-Natalia
Hromádka, Tomáš
Venue: Acta Neuropathologica Communications
Publisher: Springer Science and Business Media LLC
Published: 2019-07-05
Volume: 7
Issue: 1
Pages: 109-109
ISSN: 2051-5960 (ISSN-L)
DOI: 10.1186/s40478-019-0754-y
PMC: PMC6612163
OpenAlex: W2956146459
Cited by: 197
References: 332
Citations by year: 2026: 20 · 2025: 27 · 2024: 27 · 2023: 21 · 2022: 36 · 2021: 40 · 2020: 24 · 2019: 1 · 2018: 1
FWCI: 2.99
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Acta Neuropathologica Communications (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: SyDAD, Horizon 2020 research & innovation program (676144)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords: tauopathy, tau pathology, microglia, synaptic loss, neuroinflammation, Alzheimer's disease, progressive supranuclear palsy, chronic traumatic encephalopathy, TREM2, apolipoprotein E, microglial phagocytosis, neurodegeneration
MeSH terms: Animals, Apolipoproteins E, Humans, Membrane Glycoproteins, Receptors, Immunologic, Synapses, tau Proteins, Microglia, Tauopathies

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Intersection of pathological tau and microglia at the synapse

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