TFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading
Open accessAbstract
The progression of tau pathology in Alzheimer’s disease follows a stereotyped pattern, and recent evidence suggests a role of synaptic connections in this process. Astrocytes are well positioned at the neuronal synapse to capture and degrade extracellular tau as it transits the synapse and hence could potentially have the ability to inhibit tau spreading and delay disease progression. Our study shows increased expression and activity of Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis, in response to tau pathology in both human brains with dementia and transgenic mouse models. Exogenous TFEB expression in primary astrocytes enhances tau fibril uptake and lysosomal activity, while TFEB knockout has the reverse effect. In vivo, induced TFEB expression in astrocytes reduces pathology in the hippocampus of PS19 tauopathy mice, as well as prominently attenuates tau spreading from the ipsilateral to the contralateral hippocampus in a mouse model of tau spreading. Our study suggests that astrocytic TFEB plays a functional role in modulating extracellular tau and the propagation of neuronal tau pathology in tauopathies such as Alzheimer’s disease.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Previous studies have shown that astrocytes can internalize tau monomers, truncated pre-formed fibrils (PFFs), and tau oligomers through HSPG-independent mechanisms.
“Previous studies have shown that astrocytes can internalize tau monomers, 13 truncated pre‐formed fibrils (PFFs), 12 and tau oligomers 11 , 41 through HSPG‐independent mechanisms. 28”
From Protective mechanisms against Alzheimer's disease in APOE3‐Christchurch homozygous astrocytes (2025) · cites this paper as [12]
Citation 28 is attached to the claim that uptake occurs through HSPG-independent mechanisms. The Results section (page not available in our copy) says instead that tau fibril uptake involves interaction with cell-surface HSPGs and reports that heparin, used to inhibit that interaction, reduces fibril uptake in primary astrocytes. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredAstrocytes are active participants in tau clearance, a process critical for limiting the spread of pathological tau aggregates in AD and related tauopathies.
“astrocytes are increasingly recognized as active participants in tau clearance, a process critical for limiting the spread of pathological tau aggregates in AD and related tauopathies.”
From Protective mechanisms against Alzheimer's disease in APOE3‐Christchurch homozygous astrocytes (2025) · cites this paper as [12]
Astrocytes phagocytose extracellular tau and contribute to tau spreading through transcription factor EB.
“Similar to microglia, astrocytes can also phagocytose extracellular tau and contribute to tau spreading through transcription factor EB [435].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [435]
TFEB induces astrocytic trafficking of tau fibrils via macropinocytosis, possibly through interaction with heparan sulfate proteoglycans (HSPGs).
“TFEB induces astrocytic trafficking of tau fibrils via macropinocytosis, possibly through interaction with heparan sulfate proteoglycans (HSPGs) [200, 201].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [201]
Overexpression of TFEB in astrocytes promotes tau fibril species uptake and lysosomal activity as well as attenuates tau spreading and pathology in the hippocampus of P301S tauopathy mice.
“Overexpression of transcription factor EB (TFEB, a regulator of lysosomal biogenesis) in astrocytes promotes tau fibril species uptake and lysosomal activity as well as attenuates tau spreading and pathology in the hippocampus of P301S tauopathy mice [201] (Fig. 1).”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [201]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Neuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226 · see citing works
Genome-wide atlas of gene expression in the adult mouse brain
Lein, E. S., Hawrylycz, M. J., Ao, N., Ayres, M., Bensinger, A., Bernard, A., Boe, A. F., Boguski, M. S., Brockway, K. S., Byrnes, E. J., et al. (2007) · Nature · doi:10.1038/nature05453 · Cited by 5,572 · see citing works
TFEB Links Autophagy to Lysosomal Biogenesis
Settembre, C., Di Malta, C., Polito, V. A., Arencibia, M. G., Vetrini, F., Erdin, S., Erdin, S. U., Huynh, T., Medina, D., Colella, P., et al. (2011) · Science · doi:10.1126/science.1204592 · Cited by 3,365 · see citing works
Self-citationCahoy, J. D., Emery, B., Kaushal, A., Foo, L. C., Zamanian, J. L., Christopherson, K. S., Xing, Y., Lubischer, J. L., Krieg, P. A., Krupenko, S. A., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4178-07.2008 · Cited by 3,129 · see citing works
A Gene Network Regulating Lysosomal Biogenesis and Function
Sardiello, M., Palmieri, M., di Ronza, A., Medina, D. L., Valenza, M., Gennarino, V. A., Di Malta, C., Donaudy, F., Embrione, V., Polishchuk, R. S., et al. (2009) · Science · doi:10.1126/science.1174447 · Cited by 2,543 · see citing works
Self-citationStaging of alzheimer's disease-related neurofibrillary changes
Braak, H., & Braak, E. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00021-6 · Cited by 2,357 · see citing works
Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208 · see citing works
Self-citationTau Suppression in a Neurodegenerative Mouse Model Improves Memory Function
SantaCruz, K., Lewis, J., Spires, T., Paulson, J., Kotilinek, L., Ingelsson, M., Guimaraes, A., DeTure, M., Ramsden, M., McGowan, E., et al. (2005) · Science · doi:10.1126/science.1113694 · Cited by 2,014 · see citing works
A lysosome‐to‐nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB
Settembre, C., Zoncu, R., Medina, D. L., Vetrini, F., Erdin, S., Erdin, S. U., Huynh, T., Ferron, M., Karsenty, G., Vellard, M. C., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.32 · Cited by 1,932 · see citing works
Tripartite synapses: astrocytes process and control synaptic information
Perea, G., Navarrete, M., & Araque, A. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.05.001 · Cited by 1,820 · see citing works
Transmission and spreading of tauopathy in transgenic mouse brain
Clavaguera, F., Bolmont, T., Crowther, R. A., Abramowski, D., Frank, S., Probst, A., Fraser, G., Stalder, A. K., Beibel, M., Staufenbiel, M., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1901 · Cited by 1,803 · see citing works
Depletion of microglia and inhibition of exosome synthesis halt tau propagation
Asai, H., Ikezu, S., Tsunoda, S., Medalla, M., Luebke, J., Haydar, T., Wolozin, B., Butovsky, O., Kügler, S., & Ikezu, T. (2015) · Nature Neuroscience · doi:10.1038/nn.4132 · Cited by 1,591 · see citing works
Propagation of Tau Pathology in a Model of Early Alzheimer's Disease
de Calignon, A., Polydoro, M., Suárez-Calvet, M., William, C., Adamowicz, D. H., Kopeikina, K. J., Pitstick, R., Sahara, N., Ashe, K. H., Carlson, G. A., et al. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.033 · Cited by 1,427 · see citing works
MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB
Martina, J. A., Chen, Y., Guček, M., & Puertollano, R. (2012) · Autophagy · doi:10.4161/auto.19653 · Cited by 1,360 · see citing works
Roczniak-Ferguson, A., Petit, C. S. V., Froehlich, F., Qian, S., Ky, J., Angarola, B. L., Walther, T. C., & Ferguson, S. M. (2012) · Science Signaling · doi:10.1126/scisignal.2002790 · Cited by 1,358 · see citing works
The Mystery and Magic of Glia: A Perspective on Their Roles in Health and Disease
Barres, B. A. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.013 · Cited by 1,352 · see citing works
Propagation of Tau Misfolding from the Outside to the Inside of a Cell
Frost, B., Jacks, R. L., & Diamond, M. I. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808759200 · Cited by 1,252 · see citing works
ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy
Initiative, A. D. N., Shi, Y., Yamada, K., Liddelow, S. A., Smith, S. T., Zhao, L., Luo, W., Tsai, R. M., Spina, S., Grinberg, L. T., et al. (2017) · Nature · doi:10.1038/nature24016 · Cited by 1,220 · see citing works
Lee, J.-H., Yu, W. H., Kumar, A., Lee, S., Mohan, P. S., Peterhoff, C. M., Wolfe, D. M., Martinez-Vicente, M., Massey, A. C., Sovak, G., et al. (2010) · Cell · doi:10.1016/j.cell.2010.05.008 · Cited by 1,212 · 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
Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways
Palmieri, M., Impey, S., Kang, H., di Ronza, A., Pelz, C., Sardiello, M., & Ballabio, A. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr306 · Cited by 1,022 · see citing works
Self-citationTrans-Synaptic Spread of Tau Pathology In Vivo
Liu, L., Drouet, V., Wu, J., Witter, M. P., Small, S. A., Clelland, C. L. T., & Duff, K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031302 · Cited by 994 · see citing works
Adult mouse astrocytes degrade amyloid-β in vitro and in situ
Wyss-Coray, T., Loike, J. D., Brionne, T. C., Lu, E., Anankov, R., Yan, F., Silverstein, S. C., & Husemann, J. (2003) · Nature Medicine · doi:10.1038/nm838 · Cited by 909 · see citing works
Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds
Holmes, B. B., DeVos, S. L., Kfoury, N., Li, M., Jacks, R., Yanamandra, K., Ouidja, M. O., Brodsky, F. M., Marasa, J., Bagchi, D. P., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1301440110 · Cited by 859 · see citing works
The tripartite synapse: roles for gliotransmission in health and disease
Halassa, M. M., Fellin, T., & Haydon, P. G. (2007) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2006.12.005 · Cited by 852 · see citing works
Neuronal activity enhances tau propagation and tau pathology in vivo
Wu, J. W., Hussaini, S. A., Bastille, I. M., Rodriguez, G. A., Mrejeru, A., Rilett, K., Sanders, D. W., Cook, C., Fu, H., Boonen, R. A. C. M., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4328 · Cited by 820 · see citing works
Astrocytes: a central element in neurological diseases
Pekny, M., Pekna, M., Messing, A., Steinhäuser, C., Lee, J., Parpura, V., Hol, E. M., Sofroniew, M. V., & Verkhratsky, A. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1513-1 · Cited by 755 · see citing works
Transcriptional Activation of Lysosomal Exocytosis Promotes Cellular Clearance
Medina, D. L., Fraldi, A., Bouchè, V., Annunziata, F., Mansueto, G., Spampanato, C., Puri, C., Pignata, A., Martina, J. A., Sardiello, M., et al. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.07.016 · Cited by 708 · see citing works
Self-citationRamsden, 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
Proteopathic tau seeding predicts tauopathy in vivo
Holmes, B. B., Furman, J. L., Mahan, T. E., Yamasaki, T. R., Mirbaha, H., Eades, W. C., Belaygorod, L., Cairns, N. J., Holtzman, D. M., & Diamond, M. I. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1411649111 · Cited by 696 · see citing works
Iba, M., Guo, J. L., McBride, J. D., Zhang, B., Trojanowski, J. Q., & Lee, V. M.-Y. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.2642-12.2013 · Cited by 664 · see citing works
Self-citationPhysiological release of endogenous tau is stimulated by neuronal activity
Pooler, A. M., Phillips, E. C., Lau, D. H. W., Noble, W., & Hanger, D. P. (2013) · The EMBO Reports · doi:10.1038/embor.2013.15 · Cited by 642 · see citing works
Seeding of Normal Tau by Pathological Tau Conformers Drives Pathogenesis of Alzheimer-like Tangles
Guo, J. L., & Lee, V. M.-Y. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.209296 · Cited by 636 · see citing works
Self-citationTing, J. T., Daigle, T. L., Chen, Q., & Feng, G. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-1096-0_14 · Cited by 631 · see citing works
Prions hijack tunnelling nanotubes for intercellular spread
Gousset, K., Schiff, E., Langevin, C., Marijanovic, Z., Caputo, A., Browman, D., Chenouard, N., de Chaumont, F., Martino, A., Enninga, J., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1841 · Cited by 616 · see citing works
Yanamandra, K., Kfoury, N., Jiang, H., Mahan, T. E., Ma, S., Maloney, S. E., Wozniak, D. F., Diamond, M. I., & Holtzman, D. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.046 · Cited by 574 · see citing works
Neuronal activity regulates extracellular tau in vivo
Yamada, K., Holth, J. K., Liao, F., Stewart, F. R., Mahan, T. E., Jiang, H., Cirrito, J. R., Patel, T. K., Hochgräfe, K., Mandelkow, E., et al. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20131685 · Cited by 574 · see citing works
Trans-cellular Propagation of Tau Aggregation by Fibrillar Species
Kfoury, N., Holmes, B. B., Jiang, H., Holtzman, D. M., & Diamond, M. I. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.346072 · Cited by 552 · see citing works
Aging-related tau astrogliopathy (ARTAG): Harmonized evaluation strategy
Kovacs, G. G., Ferrer, I., Grinberg, L. T., Alafuzoff, I., Attems, J., Budka, H., Cairns, N. J., Crary, J. F., Duyckaerts, C., Ghetti, B., et al. (2016) · Acta Neuropathologica · doi:10.1007/s00401-015-1509-x · Cited by 532 · see citing works
Regulated ATP release from astrocytes through lysosome exocytosis
Zhang, Z., Chen, G., Zhou, W., Song, A., Xu, T., Luo, Q., Wang, W., Gu, X., & Duan, S. (2007) · Nature Cell Biology · doi:10.1038/ncb1620 · Cited by 525 · see citing works
Regulation of TFEB and V‐ATPases by mTORC1
Peña‐Llopis, S., Vega-Rubín-de-Celis, S., Schwartz, J. C., Wolff, N. C., Tran, T. A. T., Zou, L., Xie, X., Corey, D. R., & Brugarolas, J. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.257 · Cited by 456 · see citing works
Palmieri, M., Pal, R., Nelvagal, H. R., Lotfi, P., Stinnett, G. R., Seymour, M. L., Chaudhury, A., Bajaj, L., Bondar, V. V., Bremner, L., et al. (2017) · Nature Communications · doi:10.1038/ncomms14338 · Cited by 430 · see citing works
Self-citationNarasimhan, S., Guo, J. L., Changolkar, L., Stieber, A., McBride, J. D., Silva, L. V., He, Z., Zhang, B., Gathagan, R. J., Trojanowski, J. Q., et al. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.1230-17.2017 · Cited by 374 · see citing works
Self-citationLee, J.-H., McBrayer, M. K., Wolfe, D. M., Haslett, L. J., Kumar, A., Sato, Y., Lie, P. P. Y., Mohan, P., Coffey, E. E., Kompella, U., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.07.050 · Cited by 358 · see citing works
Yamada, K., Cirrito, J. R., Stewart, F. R., Jiang, H., Finn, M. B., Holmes, B. B., Binder, L. I., Mandelkow, E.-M., Diamond, M. I., Lee, V. M.-Y., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.2569-11.2011 · Cited by 351 · see citing works
Self-citationSelective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB
Polito, V. A., Li, H., Martini‐Stoica, H., Wang, B., Li, Y., Xu, Y., Swartzlander, D. B., Palmieri, M., di Ronza, A., Lee, V. M. ‐., et al. (2014) · EMBO Molecular Medicine · doi:10.15252/emmm.201303671 · Cited by 350 · see citing works
Self-citationAutophagy failure in A lzheimer's disease and the role of defective lysosomal acidification
Wolfe, D. M., Lee, J., Kumar, A. R., Lee, S., Orenstein, S. J., & Nixon, R. A. (2013) · European Journal of Neuroscience · doi:10.1111/ejn.12169 · Cited by 348 · see citing works
Transcription factor EB (TFEB) is a new therapeutic target for Pompe disease
Spampanato, C., Feeney, E., Li, L., Cardone, M., Lim, J., Annunziata, F., Zare, H., Polishchuk, R., Puertollano, R., Parenti, G., et al. (2013) · EMBO Molecular Medicine · doi:10.1002/emmm.201202176 · Cited by 341 · see citing works
TFEB and TFE3 cooperate in the regulation of the innate immune response in activated macrophages
Pastore, N., Brady, O. A., Diab, H. I., Martina, J. A., Sun, L., Huynh, T., Lim, J.-A., Zare, H., Raben, N., Ballabio, A., et al. (2016) · Autophagy · doi:10.1080/15548627.2016.1179405 · Cited by 331 · see citing works
Styren, S. D., Hamilton, R. L., Styren, G. C., & Klunk, W. E. (2000) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215540004800906 · Cited by 290 · see citing works
Ayuso, E., Mingozzi, F., Montané, J., León, X., Anguela, X. M., Haurigot, V., Edmonson, S. A., Africa, L. M., Zhou, S., High, K. A., et al. (2009) · Gene Therapy · doi:10.1038/gt.2009.157 · Cited by 279 · see citing works
Xiao, Q., Yan, P., Ma, X., Liu, H., Perez, R., Zhu, A., Gonzales, E., Burchett, J. M., Schuler, D. R., Cirrito, J. R., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3788-13.2014 · Cited by 266 · see citing works
Riemenschneider, M., Wagenpfeil, S., Vanderstichele, H., Otto, M., Wiltfang, J., Kretzschmar, H., Vanmechelen, E., Förstl, H., & Kurz, A. (2003) · Molecular Psychiatry · doi:10.1038/sj.mp.4001220 · Cited by 238 · see citing works
Memory and mental status correlates of modified Braak staging
Grober, E. H., Dickson, D. W., Sliwinski, M. J., Herman Buschke, L., Katz, M., Crystal, H., & Lipton, R. B. (1999) · Neurobiology of Aging · doi:10.1016/s0197-4580(99)00063-9 · Cited by 235 · see citing works
Cuervo, A. M., & Dice, J. F. (2000) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00075-9 · Cited by 215 · see citing works
Glial Inclusions in CNS Degenerative Diseases
Chin, S., & Goldman, J. E. (1996) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199605000-00001 · Cited by 208 · see citing works
Coen, K., Flannagan, R. S., Baron, S., Carraro-Lacroix, L. R., Wang, D., Vermeire, W., Michiels, C., Munck, S., Baert, V., Sugita, S., et al. (2012) · Journal of Cell Biology · doi:10.1083/jcb.201201076 · Cited by 208 · see citing works
Capsid Serotype and Timing of Injection Determines AAV Transduction in the Neonatal Mice Brain
Chakrabarty, P., Rosario, A. M., Cruz, P. E., Siemienski, Z. B., Ceballos‐Diaz, C., Crosby, K. W., Jansen, K. R., Borchelt, D., Kim, J., Jankowsky, J. L., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067680 · Cited by 201 · see citing works
Characterization of Two VQIXXK Motifs for Tau Fibrillization in Vitro
Li, W., & Lee, V. M. ‐. (2006) · Biochemistry · doi:10.1021/bi061422+ · Cited by 197 · see citing works
Self-citationBasak, J. M., Verghese, P. B., Yoon, H., Kim, J., & Holtzman, D. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.288746 · Cited by 192 · 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
TFEB regulates lysosomal proteostasis
Song, W., Wang, F., Savini, M., Ake, A., di Ronza, A., Sardiello, M., & Segatori, L. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt052 · Cited by 143 · see citing works
Self-citationNiemann-Pick Type C Disease and Alzheimer's Disease
Nixon, R. A. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63163-x · Cited by 139 · see citing works
Glial promoter selectivity following AAV-delivery to the immature brain
von Jonquieres, G., Mersmann, N., Klugmann, C. B., Harasta, A. E., Lutz, B., Teahan, O., Housley, G. D., Fröhlich, D., Krämer-Albers, E.-M., & Klugmann, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065646 · Cited by 133 · see citing works
Kovacs, G. G., Robinson, J. L., Xie, S. X., Lee, E. B., Grossman, M., Wolk, D. A., Irwin, D. J., Weintraub, D., Kim, C. F., Schuck, T., et al. (2017) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlx007 · Cited by 132 · see citing works
Self-citationDistinct Therapeutic Mechanisms of Tau Antibodies
Funk, K. E., Mirbaha, H., Jiang, H., Holtzman, D. M., & Diamond, M. I. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.657924 · Cited by 111 · see citing works
Ljungberg, M. C., Ali, Y. O., Zhu, J., Wu, C.-S., Oka, K., Zhai, R. G., & Lu, H.-C. (2012) · Human Molecular Genetics · doi:10.1093/hmg/ddr492 · Cited by 107 · cited 1× · see citing works
“AAVs were dialyzed against phosphate buffered saline without Mg2+ and Ca2+, and the titer was determined by real time PCR as described previously (Ljungberg et al., 2012).”
MethodLalo, U., Palygin, O., Verkhratsky, A., Grant, S. G. N., & Pankratov, Y. V. (2016) · Scientific Reports · doi:10.1038/srep33609 · Cited by 106 · see citing works
Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy
Yanamandra, K., Patel, T. K., Jiang, H., Schindler, S., Ulrich, J. D., Boxer, A. L., Miller, B. L., Kerwin, D. R., Gallardo, G., Stewart, F., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aal2029 · Cited by 100 · see citing works
High prevalence of thorn-shaped astrocytes in the aged human medial temporal lobe
Schultz, C., Ghebremedhin, E., Tredici, K. D., Rüb, U., & Braak, H. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(03)00113-1 · Cited by 91 · see citing works
Immunohistochemical detection of dityrosine in lipofuscin pigments in the aged human brain
Kato, Y., Maruyama, W., Naoi, M., Hashizume, Y., & Osawa, T. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)01372-6 · Cited by 90 · see citing works
Protein astrogliopathies in human neurodegenerative diseases and aging
Kovács, G. G., Lee, V. M., & Trojanowski, J. Q. (2017) · Brain Pathology · doi:10.1111/bpa.12536 · Cited by 89 · see citing works
Self-citationTau-Focused Immunotherapy for Alzheimers Disease and Related Tauopathies
Sigurdsson, E. M. (2009) · Current Alzheimer Research · doi:10.2174/156720509789207930 · Cited by 87 · see citing works
Synaptic Regulation of a Thalamocortical Circuit Controls Depression-Related Behavior
Miller, O. H., Bruns, A., Ammar, I. B., Mueggler, T., & Hall, B. J. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.002 · Cited by 69 · see citing works
Swartzlander, D. B., Propson, N. E., Roy, E. R., Saito, T., Saido, T. C., Wang, B., & Zheng, H. (2018) · JCI Insight · doi:10.1172/jci.insight.121109 · Cited by 54 · see citing works
Self-citationLi, Y., Cheng, D., Cheng, R., Zhu, X., Wan, T., Liu, J., & Zhang, R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0099939 · Cited by 51 · see citing works
Oyama, F., Murakami, N., & Ihara, Y. (1998) · Neuroscience Research · doi:10.1016/s0168-0102(98)00020-0 · Cited by 47 · see citing works
Chen, F., Moran, J., Zhang, Y., Ates, K. M., Yu, D., Schrader, L. A., Das, P. M., Jones, F. E., & Hall, B. J. (2016) · The Journal of Physiology · doi:10.1113/jp271953 · Cited by 40 · see citing works
Self-citationA seeding based cellular assay of tauopathy
Xu, Y., Martini‐Stoica, H., & Zheng, H. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0100-9 · Cited by 26 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Synergy between amyloid-β and tau in Alzheimer’s disease
Busche, M. A., & Hyman, B. T. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0687-6 · Cited by 1,242 · see citing works
Grubman, A., Chew, G., Ouyang, J. F., Sun, G., Choo, X. Y., McLean, C., Simmons, R. K., Buckberry, S., Vargas-Landin, D. B., Poppe, D., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0539-4 · Cited by 956 · see citing works
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
Guo, T., Zhang, D., Zeng, Y., Huang, T. Y., Xu, H., & Zhao, Y. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00391-7 · Cited by 994 · see citing works
Interaction between Aβ and Tau in the Pathogenesis of Alzheimer’s Disease
Zhang, H., Wei, W., Zhao, M., Ma, L., Jiang, X., Pei, H., Cao, Y., & Li, H. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.57078 · Cited by 689 · see citing works
Protein transmission in neurodegenerative disease
Peng, C., Trojanowski, J. Q., & Lee, V. M.-Y. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0333-7 · Cited by 625 · see citing works
Self-citationTau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation
Chen, Y., & Yu, Y. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02853-3 · Cited by 516 · see citing works
“Overexpression of transcription factor EB (TFEB, a regulator of lysosomal biogenesis) in astrocytes promotes tau fibril species uptake and lysosomal activity as well as attenuates tau spreading and pathology in the hippocampus of P301S tauopathy mice [201] (Fig.”
BackgroundMechanisms of secretion and spreading of pathological tau protein
Brunello, C. A., Merezhko, M., Uronen, R.-L., & Huttunen, H. J. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03349-1 · Cited by 304 · see citing works
Intersection of pathological tau and microglia at the synapse
Vogels, T., Murgoci, A.-N., & Hromádka, T. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0754-y · Cited by 197 · see citing works
Experimental evidence for the age dependence of tau protein spread in the brain
Wegmann, S., Bennett, R. E., Delorme, L., Robbins, A. B., Hu, M., MacKenzie, D., Kirk, M. J., Schiantarelli, J., Tunio, N., Amaral, A. C., et al. (2019) · Science Advances · doi:10.1126/sciadv.aaw6404 · Cited by 144 · see citing works
Extracellular Monomeric Tau Is Internalized by Astrocytes
Perea, J. R., López, E., Díez-Ballesteros, J. C., Ávila, J., Hernández, F., & Bolós, M. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00442 · Cited by 114 · see citing works
Microglia and Astrocytes in Alzheimer’s Disease: Significance and Summary of Recent Advances
Deng, Q., Wu, C., Parker, E., Liu, T. C.-Y., Duan, R., & Yang, L. (2023) · Aging and disease · doi:10.14336/ad.2023.0907 · Cited by 102 · see citing works
Filamentous recombinant human Tau activates primary astrocytes via an integrin receptor complex
Wang, P., & Ye, Y. (2021) · Nature Communications · doi:10.1038/s41467-020-20322-w · Cited by 93 · see citing works
Microglia: Friend and foe in tauopathy
Odfalk, K. F., Bieniek, K. F., & Hopp, S. C. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102306 · Cited by 60 · see citing works
In Vivo Assessment of Neuroinflammation in <scp>4‐Repeat</scp> Tauopathies
Palleis, C., Sauerbeck, J., Beyer, L., Harris, S., Schmitt, J., Morenas‐Rodriguez, E., Finze, A., Nitschmann, A., Ruch‐Rubinstein, F., Eckenweber, F., et al. (2021) · Movement Disorders · doi:10.1002/mds.28395 · Cited by 62 · see citing works
Pharmacological modulation of autophagy for Alzheimer's disease therapy: Opportunities and obstacles
Deng, Z., Dong, Y., Zhou, X., Lu, J.-H., & Yue, Z. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.12.009 · Cited by 58 · see citing works
Comerota, M. M., Gedam, M., Xiong, W., Jin, F., Deng, L., Wang, M. C., Wang, J., & Zheng, H. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00648-x · Cited by 31 · see citing works
Self-citationJaye, S., Sandau, U. S., & Saugstad, J. A. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1378576 · Cited by 26 · see citing works
Tunneling nanotubes: A novel pharmacological target for neurodegenerative diseases?
Wang, X.-T., Sun, H., Chen, N.-H., & Yuan, Y.-H. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105541 · Cited by 22 · see citing works
Continuous Monitoring of Tau-Induced Neurotoxicity in Patient-Derived iPSC-Neurons
Oakley, D. H., Klickstein, N., Commins, C., Chung, M., Dujardin, S., Bennett, R. E., Hyman, B. T., & Frosch, M. P. (2021) · The Journal of Neuroscience · doi:10.1523/jneurosci.2590-20.2021 · Cited by 18 · see citing works
Protective mechanisms against Alzheimer's disease in APOE3‐Christchurch homozygous astrocytes
Tian, X., Rivera, E. K., Hwang, I., Nikitina, A. A., Smith, J. A., Cho, Y. J., Sala‐Jarque, J., DuBose, A., Andriola, C., Gollan‐Myers, T., et al. (2025) · Alzheimer's & Dementia · doi:10.1002/alz.70589 · Cited by 7 · see citing works
- Authors
- 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., Sardiello, M., & Zheng, H.
- Affiliations
- Huffington Center on Aging, Baylor College of Medicine, Houston, TX 1
- Baylor College of Medicine (US)
- University of Pennsylvania (US)
- Corresponding author
- Zheng, Hui
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2018-08-14
- Volume
- 215
- Issue
- 9
- Pages
- 2355-2377
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC6122971
- OpenAlex
- W2887230896
- Cited by
- 253
- References
- 81
- Citations by year
- 2026: 26 · 2025: 23 · 2024: 40 · 2023: 32 · 2022: 30 · 2021: 45 · 2020: 34 · 2019: 22
- FWCI
- 17.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (P30 AI036211, P30 CA125123, S10 RR024574)
- NIH (P30 CA125123, R01 NS093652, R01 AG020670, RF1 AG054111, ADCC AG010124, FTD PPG AG17586, F30 AG050412)
- Wyncote Foundation
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- TFEB, astrocytes, tau propagation, extracellular tau, lysosomal biogenesis, Alzheimer's disease, tauopathy, hippocampus, PS19 mice, transgenic mouse model
- MeSH terms
- Alzheimer Disease, Animals, Astrocytes, Disease Models, Animal, Hippocampus, Lysosomes, Synapses, tau Proteins, Mice, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Gene Knockdown Techniques
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 ›
Are you an author, or do you see a problem with this page? Request a review
