Synthetic Tau Fibrils Mediate Transmission of Neurofibrillary Tangles in a Transgenic Mouse Model of Alzheimer's-Like Tauopathy
Open accessAbstract
Tauopathies, including Alzheimer's disease (AD) and frontotemporal lobar degeneration with tau pathologies, are neurodegenerative diseases characterized by neurofibrillary tangles (NFTs) comprising filamentous tau protein. Although emerging evidence suggests that tau pathology may be transmitted, we demonstrate here that synthetic tau fibrils are sufficient to transmit tau inclusions in a mouse model. Specifically, intracerebral inoculation of young PS19 mice overexpressing mutant human tau (P301S) with synthetic preformed fibrils (pffs) assembled from recombinant full-length tau or truncated tau containing four microtubule binding repeats resulted in rapid induction of NFT-like inclusions that propagated from injected sites to connected brain regions in a time-dependent manner. Interestingly, injection of tau pffs into either hippocampus or striatum together with overlaying cortex gave rise to distinct pattern of spreading. Moreover, unlike tau pathology that spontaneously develops in old PS19 mice, the pff-induced tau inclusions more closely resembled AD NFTs because they were Thioflavin S positive, acetylated, and more resistant to proteinase K digestion. Together, our study demonstrates that synthetic tau pffs alone are capable of inducing authentic NFT-like tau aggregates and initiating spreading of tau pathology in a tauopathy mouse model.
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?
Mice have primarily monocular vision, with >95% of retinal ganglion cells projecting into the contralateral side of the brain, allowing the unaffected side to serve as an internal control.
“As mice have primarily monocular vision, with >95% of RGCs projecting into the contralateral side of the brain, the unaffected side of the visual system can serve as an internal control 26, 27”
From Amyloid-beta induced retrograde axonal degeneration in a mouse tauopathy model (2019) · cites this paper as [26]
The Materials and Methods section describes comparing injected and contralateral hippocampi, and the Results report tau pathology in both; neither passage concerns the visual system. Searches for retinal ganglion cells, monocular vision, and the claimed >95% contralateral projection found no passage addressing those points or the proposed visual-system control. Page numbers were not available in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredSeeded synthetic tau fibrils, or brain extracts from tau transgenic mice or human patients with tauopathy injected into the brain of tau transgenic or WT mice induce pathological tau spreading at sites distal to the injection site.
“seeded synthetic tau fibrils, or brain extracts from tau transgenic mice or human patients with tauopathy injected into the brain of tau transgenic or WT mice was found to induce pathological tau spreading at sites distal to the injection site [232–235].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [233]
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
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · cited 1× · see citing works
“In AD brains, NFT progressively accumulate in a well-defined stereotypical pattern, with pathology first emerging in entorhinal cortex, followed by hippocampus, and eventually neocortex (Braak and Braak, 1991).”
BackgroundThe Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859 · 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
Aston-Jones, G., & Cohen, J. D. (2005) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.28.061604.135709 · Cited by 4,472 · see citing works
Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
Hutton, M., Lendon, C. L., Rizzu, P., Baker, M., Froelich, S., Houlden, H., Pickering-Brown, S., Chakraverty, S., Isaacs, A., Grover, A., et al. (1998) · Nature · doi:10.1038/31508 · Cited by 3,498 · see citing works
Self-citationBerridge, C. W., & Waterhouse, B. D. (2003) · Brain Research Reviews · doi:10.1016/s0165-0173(03)00143-7 · Cited by 2,529 · see citing works
Lee, V. M.-Y., Goedert, M., & Trojanowski, J. Q. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1121 · Cited by 2,480 · see citing works
Self-citationSynapse 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-mediated neurodegeneration in Alzheimer’s disease and related disorders
Ballatore, C., Lee, V. M.-Y., & Trojanowski, J. Q. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2194 · Cited by 2,174 · see citing works
Self-citationNucleus locus ceruleus: new evidence of anatomical and physiological specificity
Foote, S. L., Bloom, F. E., & Aston-Jones, G. (1983) · Physiological Reviews · doi:10.1152/physrev.1983.63.3.844 · Cited by 1,901 · 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
Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease
Gómez‐Isla, T., Hollister, R., West, H., Mui, S., Growdon, J. H., Petersen, R. C., Parisi, J. E., & Hyman, B. T. (1997) · Annals of Neurology · doi:10.1002/ana.410410106 · Cited by 1,489 · see citing works
Mutation in the tau gene in familial multiple system tauopathy with presenile dementia
Spillantini, M. G., Murrell, J. R., Goedert, M., Farlow, M. R., Klug, A., & Ghetti, B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7737 · Cited by 1,474 · 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
A68: a Major Subunit of Paired Helical Filaments and Derivatized Forms of Normal Tau
Lee, V. M.-Y., Balin, B. J., Otvos, L., & Trojanowski, J. Q. (1991) · Science · doi:10.1126/science.1899488 · Cited by 1,418 · see citing works
Self-citationPropagation 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
Luk, K. C., Kehm, V. M., Zhang, B., O’Brien, P., Trojanowski, J. Q., & Lee, V. M. ‐. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20112457 · Cited by 1,087 · see citing works
Self-citationGoedert, M., Jakes, R., Spillantini, M. G., Hasegawa, M., Smith, M. J., & Crowther, R. A. (1996) · Nature · doi:10.1038/383550a0 · Cited by 1,036 · see citing works
Trans-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
Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein tau.
Drechsel, D. N., Hyman, A. A., Cobb, M. H., & Kirschner, M. W. (1992) · Molecular Biology of the Cell · doi:10.1091/mbc.3.10.1141 · Cited by 971 · see citing works
Exogenous Induction of Cerebral ß-Amyloidogenesis Is Governed by Agent and Host
Meyer-Luehmann, M., Coomaraswamy, J., Bolmont, T., Kaeser, S., Schaefer, C., Kilger, E., Neuenschwander, A., Abramowski, D., Frey, P., Jaton, A. L., et al. (2006) · Science · doi:10.1126/science.1131864 · Cited by 971 · see citing works
Acetylation of Tau Inhibits Its Degradation and Contributes to Tauopathy
Min, S.-W., Cho, S.-H., Zhou, Y., Schroeder, S., Haroutunian, V., Seeley, W. W., Huang, E. J., Shen, Y., Masliah, E., Mukherjee, C., et al. (2010) · Neuron · doi:10.1016/j.neuron.2010.08.044 · Cited by 949 · see citing works
The pathological process underlying Alzheimer’s disease in individuals under thirty
Braak, H., & Del Tredici, K. (2011) · Acta Neuropathologica · doi:10.1007/s00401-010-0789-4 · Cited by 812 · see citing works
Some morphometric aspects of the brain in senile dementia of the alzheimer type
Terry, R. D., Peck, A., DeTeresa, R., Schechter, R., & Horoupian, D. S. (1981) · Annals of Neurology · doi:10.1002/ana.410100209 · Cited by 801 · see citing works
The Brain Nucleus Locus Coeruleus: Restricted Afferent Control of a Broad Efferent Network
Aston‐Jones, G., Ennis, M. J., Pieribone, V. A., Nickell, W. T., & Shipley, M. T. (1986) · Science · doi:10.1126/science.3775363 · Cited by 778 · see citing works
The acetylation of tau inhibits its function and promotes pathological tau aggregation
Cohen, T. J., Guo, J. L., Hurtado, D. E., Kwong, L. K., Mills, I. P., Trojanowski, J. Q., & Lee, V. M. Y. (2011) · Nature Communications · doi:10.1038/ncomms1255 · Cited by 724 · see citing works
Self-citationPost-translational modifications of tau protein: Implications for Alzheimer's disease
Martin, L., Latypova, X., & Terro, F. (2011) · Neurochemistry International · doi:10.1016/j.neuint.2010.12.023 · Cited by 645 · 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-citationPeripherally Applied Aβ-Containing Inoculates Induce Cerebral β-Amyloidosis
Eisele, Y. S., Obermüller, U., Heilbronner, G., Baumann, F., Kaeser, S. A., Wolburg, H., Walker, L. C., Staufenbiel, M., Heikenwalder, M., & Jucker, M. (2010) · Science · doi:10.1126/science.1194516 · Cited by 568 · 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
Disease‐specific patterns of locus coeruleus cell loss
German, D. C., Manaye, K. F., White, C. L., Woodward, D. J., McIntire, D. D., Smith, W. K., Kalaria, R. N., & Mann, D. M. A. (1992) · Annals of Neurology · doi:10.1002/ana.410320510 · Cited by 512 · see citing works
Alzheimer brain-derived tau oligomers propagate pathology from endogenous tau
Lasagna-Reeves, C. A., Castillo-Carranza, D. L., Sengupta, U., Guerrero-Munoz, M. J., Kiritoshi, T., Neugebauer, V., Jackson, G. R., & Kayed, R. (2012) · Scientific Reports · doi:10.1038/srep00700 · Cited by 502 · see citing works
Post-translational modifications of tau protein in Alzheimer’s disease
Gong, C.-X., Liu, F., Grundke-Iqbal, I., & Iqbal, K. (2005) · Journal of Neural Transmission · doi:10.1007/s00702-004-0221-0 · Cited by 437 · see citing works
Noradrenergic mechanisms in neurodegenerative diseases: a theory
Marien, M. R., Colpaert, F. C., & Rosenquist, A. C. (2004) · Brain Research Reviews · doi:10.1016/j.brainresrev.2004.02.002 · Cited by 411 · see citing works
Zhang, B., Carroll, J., Trojanowski, J. Q., Yao, Y., Iba, M., Potuzak, J. S., Hogan, A.-M. L., Xie, S. X., Ballatore, C., Smith, A. B., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.4922-11.2012 · Cited by 401 · see citing works
Self-citationPurified and synthetic Alzheimer’s amyloid beta (Aβ) prions
Stöhr, J., Watts, J. C., Mensinger, Z. L., Oehler, A., Grillo, S. K., DeArmond, S. J., Prusiner, S. B., & Giles, K. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1206555109 · Cited by 359 · see citing works
Alzheimer’s pathogenesis: is there neuron-to-neuron propagation?
Braak, H., & Tredici, K. D. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0825-z · Cited by 359 · see citing works
Acetylated tau, a novel pathological signature in Alzheimer's disease and other tauopathies
Irwin, D. J., Cohen, T. J., Grossman, M., Arnold, S. E., Xie, S. X., Lee, V. M.-Y., & Trojanowski, J. Q. (2012) · Brain · doi:10.1093/brain/aws013 · Cited by 281 · see citing works
Self-citationCarroll, J. C., Iba, M., Bangasser, D. A., Valentino, R. J., James, M. J., Brunden, K. R., Lee, V. M. ‐., & Trojanowski, J. Q. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3836-11.2011 · Cited by 256 · see citing works
Self-citationAnionic Micelles and Vesicles Induce Tau Fibrillization in Vitro
Chirita, C. N., Necula, M., & Kuret, J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301663200 · Cited by 244 · see citing works
Tubulin requires tau for growth onto microtubule initiating sites.
Witman, G. B., Cleveland, D. W., Weingarten, M. D., & Kirschner, M. W. (1976) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.73.11.4070 · Cited by 238 · see citing works
Hurtado, D. E., Molina-Porcel, L., Iba, M., Aboagye, A. K., Paul, S. M., Trojanowski, J. Q., & Lee, V. M.-Y. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.100346 · Cited by 222 · see citing works
Self-citationRapid Anionic Micelle-mediated α-Synuclein Fibrillization in Vitro
Necula, M., Chirita, C. N., & Kuret, J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308231200 · Cited by 211 · see citing works
Developing therapeutic approaches to tau, selected kinases, and related neuronal protein targets
Lee, V. M.-Y., Brunden, K. R., Hutton, M., & Trojanowski, J. Q. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006437 · Cited by 122 · see citing works
Self-citationAlterations in the locus coeruleus in dementias of Alzheimer's and Parkinson's disease
Chan‐Palay, V. (1991) · Progress in brain research · doi:10.1016/s0079-6123(08)63839-x · Cited by 84 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
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
Self-propagation of pathogenic protein aggregates in neurodegenerative diseases
Jucker, M., & Walker, L. C. (2013) · Nature · doi:10.1038/nature12481 · Cited by 1,663 · see citing works
Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases
Soto, C., & Pritzkow, S. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0235-9 · Cited by 1,180 · see citing works
Tau pathology and neurodegeneration
Spillantini, M. G., & Goedert, M. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70090-5 · Cited by 1,133 · 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
Distinct Tau Prion Strains Propagate in Cells and Mice and Define Different Tauopathies
Sanders, D. W., Kaufman, S. K., DeVos, S. L., Sharma, A. M., Mirbaha, H., Li, A., Barker, S. J., Foley, A. C., Thorpe, J. R., Serpell, L. C., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.04.047 · Cited by 986 · 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
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 sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans
Holth, J. K., Fritschi, S. K., Wang, C., Pedersen, N. P., Cirrito, J. R., Mahan, T. E., Finn, M. B., Manis, M., Geerling, J. C., Fuller, P. M., et al. (2019) · Science · doi:10.1126/science.aav2546 · Cited by 813 · see citing works
Spreading of pathology in neurodegenerative diseases: a focus on human studies
Brettschneider, J., Tredici, K. D., Lee, V. M.-Y., & Trojanowski, J. Q. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3887 · Cited by 790 · see citing works
Self-citationProteopathic 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
Protein misfolding in neurodegenerative diseases: Implications and strategies
Sweeney, P., Park, H., Baumann, M., Dunlop, J., Frydman, J., Kopito, R., McCampbell, A., Leblanc, G., Venkateswaran, A., Nurmi, A., et al. (2017) · Translational Neurodegeneration · doi:10.1186/s40035-017-0077-5 · Cited by 675 · see citing works
Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases
Guo, J. L., & Lee, V. M. Y. (2014) · Nature Medicine · doi:10.1038/nm.3457 · Cited by 641 · see citing works
Self-citationArendt, T., Stieler, J. T., & Holzer, M. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.08.018 · Cited by 609 · see citing works
He, Z., Guo, J. L., McBride, J. D., Narasimhan, S., Kim, H., Changolkar, L., Zhang, B., Gathagan, R. J., Yue, C., Dengler, C., et al. (2018) · Nature Medicine · doi:10.1038/nm.4443 · Cited by 645 · see citing works
Self-citationProtein 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-citationYanamandra, 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
At the interface of sensory and motor dysfunctions and Alzheimer’s disease.
Albers, M. W., Gilmore, G. C., Kaye, J., Murphy, C., Wingfield, A., Bennett, D. A., Boxer, A. L., Buchman, A. S., Cruickshanks, K. J., Devanand, D. P., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2014.04.514 · Cited by 589 · see citing works
Self-citationTau Kinetics in Neurons and the Human Central Nervous System
Sato, C., Barthélemy, N. R., Mawuenyega, K. G., Patterson, B. W., Gordon, B. A., Jockel-Balsarotti, J., Sullivan, M., Crisp, M. J., Kasten, T., Kirmess, K. M., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.02.015 · Cited by 586 · see citing works
Propagation and spread of pathogenic protein assemblies in neurodegenerative diseases
Jucker, M., & Walker, L. C. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0238-6 · Cited by 450 · see citing works
Tau molecular diversity contributes to clinical heterogeneity in Alzheimer’s disease
Dujardin, S., Commins, C., Lathuiliere, A., Beerepoot, P., Fernandes, A. R., Kamath, T. V., De Los Santos, M. B., Klickstein, N., Corjuc, D. L., Corjuc, B. T., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0938-9 · Cited by 438 · see citing works
Biology and Genetics of Prions Causing Neurodegeneration
Prusiner, S. B. (2013) · Annual Review of Genetics · doi:10.1146/annurev-genet-110711-155524 · Cited by 455 · see citing works
The Autophagy–Lysosomal Pathway in Neurodegeneration: A TFEB Perspective
Martini-Stoica, H., Xu, Y., Ballabio, A., & Zheng, H. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.02.002 · Cited by 436 · see citing works
Guo, J. L., Narasimhan, S., Changolkar, L., He, Z., Stieber, A., Zhang, B., Gathagan, R. J., Iba, M., McBride, J. D., Trojanowski, J. Q., et al. (2016) · Journal of Experimental Medicine · doi:10.1084/jem.20160833 · Cited by 440 · see citing works
Self-citationGlial contributions to neurodegeneration in tauopathies
Leyns, C. E. G., & Holtzman, D. M. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0192-x · Cited by 409 · see citing works
What is the evidence that tau pathology spreads through prion-like propagation?
Mudher, A., Colin, M., Dujardin, S., Medina, M., Dewachter, I., Alavi Naini, S. M., Mandelkow, E.-M., Mandelkow, E., Buée, L., Goedert, M., et al. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0488-7 · Cited by 384 · see citing works
Takeda, S., Wegmann, S., Cho, H., DeVos, S. L., Commins, C., Roe, A. D., Nicholls, S. B., Carlson, G. A., Pitstick, R., Nobuhara, C. K., et al. (2015) · Nature Communications · doi:10.1038/ncomms9490 · Cited by 371 · see citing works
Neurodegenerative Diseases: Expanding the Prion Concept
Walker, L. C., & Jucker, M. (2015) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071714-033828 · Cited by 361 · see citing works
Microglial NF-κB drives tau spreading and toxicity in a mouse model of tauopathy
Wang, C., Fan, L., Khawaja, R. R., Liu, B., Zhan, L., Kodama, L., Chin, M., Li, Y., Le, D., Zhou, Y., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29552-6 · Cited by 333 · see citing works
Like prions: the propagation of aggregated tau and α-synuclein in neurodegeneration
Goedert, M., Masuda-Suzukake, M., & Falcon, B. (2017) · Brain · doi:10.1093/brain/aww230 · Cited by 323 · see citing works
Tau Oligomers: Cytotoxicity, Propagation, and Mitochondrial Damage
Shafiei, S. S., Guerrero-Muñoz, M. J., & Castillo-Carranza, D. L. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00083 · Cited by 314 · see citing works
Mechanisms 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
Synaptic Tau Seeding Precedes Tau Pathology in Human Alzheimer’s Disease Brain
DeVos, S. L., Corjuc, B. T., Oakley, D. H., Nobuhara, C. K., Bannon, R. N., Chase, A., Commins, C., Gonzalez, J. A., Dooley, P. M., Frosch, M. P., et al. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00267 · Cited by 285 · 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
Self-citationRole of tau protein in Alzheimer’s disease: The prime pathological player
Muralidar, S., Ambi, S. V., Sekaran, S., Thirumalai, D., & Palaniappan, B. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.07.327 · Cited by 278 · see citing works
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
The human connectome in Alzheimer disease — relationship to biomarkers and genetics
Yu, M., Sporns, O., & Saykin, A. J. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00529-1 · Cited by 265 · see citing works
Usenovic, M., Niroomand, S., Drolet, R. E., Yao, L., Gaspar, R. C., Hatcher, N. G., Schachter, J., Renger, J. J., & Parmentier-Batteur, S. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.1523-15.2015 · Cited by 245 · 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
Models of β-amyloid induced Tau-pathology: The long and “folded” road to understand the mechanism
Stancu, I.-C., Vasconcelos, B., Terwel, D., & Dewachter, I. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-51 · Cited by 256 · see citing works
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
Porta, S., Xu, Y., Restrepo, C. R., Kwong, L. K., Zhang, B., Brown, H. J., Lee, E. B., Trojanowski, J. Q., & Lee, V. M.-Y. (2018) · Nature Communications · doi:10.1038/s41467-018-06548-9 · Cited by 248 · see citing works
Self-citationMirbaha, H., Holmes, B. B., Sanders, D. W., Bieschke, J., & Diamond, M. I. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.652693 · Cited by 215 · see citing works
Iba, M., McBride, J. D., Guo, J. L., Zhang, B., Trojanowski, J. Q., & Lee, V. M.-Y. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1458-4 · Cited by 223 · see citing works
Self-citationPeeraer, E., Bottelbergs, A., Van Kolen, K., Stancu, I.-C., Vasconcelos, B., Mahieu, M., Duytschaever, H., Ver Donck, L., Torremans, A., Sluydts, E., et al. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.08.032 · Cited by 214 · see citing works
Self-citationGoedert, M., & Spillantini, M. G. (2017) · Molecular Brain · doi:10.1186/s13041-017-0298-7 · Cited by 213 · see citing works
Traumatic Brain Injury Induces Tau Aggregation and Spreading
Edwards, G., Zhao, J., Dash, P. K., Soto, C., & Moreno-Gonzalez, I. (2020) · Journal of Neurotrauma · doi:10.1089/neu.2018.6348 · Cited by 195 · 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
BIN1 favors the spreading of Tau via extracellular vesicles
Crotti, A., Sait, H. R., McAvoy, K. M., Estrada, K., Ergun, A., Szak, S., Marsh, G., Jandreski, L., Peterson, M., Reynolds, T. L., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-45676-0 · Cited by 171 · see citing works
Jin, M., Xu, R., Wang, L., Alam, M. M., Ma, Z., Zhu, S., Martini, A. C., Jadali, A., Bernabucci, M., Xie, P., et al. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.06.007 · Cited by 174 · 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
Invited review: Prion‐like transmission and spreading of tau pathology
Clavaguera, F., Hench, J., Goedert, M., & Tolnay, M. (2015) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12197 · Cited by 156 · see citing works
Stancu, I.-C., Vasconcelos, B., Ris, L., Wang, P., Villers, A., Peeraer, E., Buist, A., Terwel, D., Baatsen, P., Oyelami, T., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1413-4 · Cited by 143 · see citing works
Avila, J., Jiménez, J. S., Sayas, C. L., Bolós, M., Zabala, J. C., Rivas, G., & Hernández, F. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00262 · Cited by 140 · see citing works
Intercellular Spread of Protein Aggregates in Neurodegenerative Disease
Davis, A. A., Leyns, C. E. G., & Holtzman, D. M. (2018) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100617-062636 · Cited by 131 · see citing works
Removing endogenous tau does not prevent tau propagation yet reduces its neurotoxicity
Wegmann, S., Maury, E. A., Kirk, M. J., Saqran, L., Roe, A., DeVos, S. L., Nicholls, S., Fan, Z., Takeda, S., Cagsal‐Getkin, O., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201592748 · Cited by 132 · see citing works
Lee, S.-H., Le Pichon, C. E., Adolfsson, O., Gafner, V., Pihlgren, M., Lin, H., Solanoy, H., Brendza, R., Ngu, H., Foreman, O., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.06.099 · Cited by 125 · see citing works
Jiang, T., Tan, L., Zhu, X.-C., Zhou, J.-S., Cao, L., Tan, M.-S., Wang, H.-F., Chen, Q., Zhang, Y.-D., & Yu, J.-T. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.08.019 · Cited by 111 · see citing works
Ando, K., Maruko-Otake, A., Ohtake, Y., Hayashishita, M., Sekiya, M., & Iijima, K. M. (2016) · PLOS Genetics · doi:10.1371/journal.pgen.1005917 · Cited by 105 · see citing works
Dai, C.-L., Hu, W., Tung, Y. C., Liu, F., Gong, C.-X., & Iqbal, K. (2018) · Alzheimer's Research & Therapy · doi:10.1186/s13195-018-0341-7 · Cited by 99 · 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
Ahnaou, A., Moechars, D., Raeymaekers, L., Biermans, R., Manyakov, N. V., Bottelbergs, A., Wintmolders, C., Van Kolen, K., Van De Casteele, T., Kemp, J. A., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-13839-6 · Cited by 98 · see citing works
Baker, S., Polanco, J. C., & Götz, J. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-160371 · Cited by 98 · see citing works
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
α-Synuclein Oligomers Induce a Unique Toxic Tau Strain
Castillo-Carranza, D. L., Guerrero-Muñoz, M. J., Sengupta, U., Gerson, J. E., & Kayed, R. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.12.018 · Cited by 84 · see citing works
Matsumoto, S.-E., Motoi, Y., Ishiguro, K., Tabira, T., Kametani, F., Hasegawa, M., & Hattori, N. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv351 · Cited by 66 · 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
Molecular mechanism of prion‐like tau‐induced neurodegeneration
Alonso, A. D., Beharry, C., Corbo, C. P., & Cohen, L. S. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.12.014 · Cited by 53 · see citing works
Malpetti, M., Jones, P. S., Cope, T. E., Holland, N., Naessens, M., Rouse, M. A., Rittman, T., Savulich, G., Whiteside, D. J., Street, D., et al. (2023) · Annals of Neurology · doi:10.1002/ana.26543 · Cited by 53 · see citing works
Perspectives for New and More Efficient Multifunctional Ligands for Alzheimer′s Disease Therapy
Zagórska, A., & Jaromin, A. (2020) · Molecules · doi:10.3390/molecules25153337 · Cited by 51 · see citing works
NPT088 reduces both amyloid‐β and tau pathologies in transgenic mice
Levenson, J. M., Schroeter, S., Carroll, J. C., Cullen, V., Asp, E., Proschitsky, M., Chung, C. H. ‐., Gilead, S., Nadeem, M., Dodiya, H. B., et al. (2016) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2016.06.004 · Cited by 47 · see citing works
Johnson, N. R., Yuan, P., Castillo, E., Lopez, T. P., Yue, W., Bond, A., Rivera, B. M., Sullivan, M. C., Hirouchi, M., Giles, K., et al. (2023) · Nature Communications · doi:10.1038/s41467-022-35753-w · Cited by 46 · see citing works
Seizures are a druggable mechanistic link between TBI and subsequent tauopathy.
Alyenbaawi, H., Kanyo, R., Locskai, L. F., Kamali-Jamil, R., DuVal, M. G., Bai, Q., Wille, H., Burton, E. A., & Allison, W. T. (2021) · eLife · doi:10.7554/elife.58744 · Cited by 40 · see citing works
Regional vulnerability and spreading of hyperphosphorylated tau in seeded mouse brain
Detrez, J. R., Maurin, H., Van Kolen, K., Willems, R., Colombelli, J., Lechat, B., Roucourt, B., Van Leuven, F., Baatout, S., Larsen, P., et al. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.03.010 · Cited by 39 · see citing works
Zimmer, E. R., Leuzy, A., Bhat, V., Gauthier, S., & Rosa-Neto, P. (2014) · Translational Neurodegeneration · doi:10.1186/2047-9158-3-6 · Cited by 30 · see citing works
Amyloid-beta induced retrograde axonal degeneration in a mouse tauopathy model
Nishioka, C., Liang, H.-F., Barsamian, B., & Sun, S.-W. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.01.007 · Cited by 30 · see citing works
George, S., Rönnbäck, A., Gouras, G. K., Petit, G. H., Grueninger, F., Winblad, B., Graff, C., & Brundin, P. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-17 · Cited by 23 · see citing works
Postmortem Interval Leads to Loss of Disease-Specific Signatures in Brain Tissue
Olney, K. C., Gibson, K. A., Cadiz, M. P., Rahimzadeh, N., Swarup, V., & Fryer, J. D. (2025) · eneuro · doi:10.1523/eneuro.0505-24.2025 · Cited by 22 · see citing works
A review of proposed mechanisms for neurodegenerative disease
Kelser, B. M., Teichner, E. M., Subtirelu, R. C., & Hoss, K. N. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1370580 · Cited by 20 · see citing works
- Authors
- Iba, M., Guo, J. L., McBride, J. D., Zhang, B., Trojanowski, J. Q., & Lee, V. M.-Y.
- Affiliations
- University of Pennsylvania (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-01-16
- Volume
- 33
- Issue
- 3
- Pages
- 1024-1037
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3575082
- OpenAlex
- W2033672635
- Cited by
- 664
- References
- 45
- Citations by year
- 2026: 23 · 2025: 45 · 2024: 45 · 2023: 33 · 2022: 48 · 2021: 74 · 2020: 66 · 2019: 62 · 2018: 46 · 2017: 51 · 2016: 49 · 2015: 48 · 2014: 47 · 2013: 27
- FWCI
- 39.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cure Alzheimer's Fund
- National Institute on Aging (P01AG017586, AG17586)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Keywords
- tauopathy, Alzheimer's disease, neurofibrillary tangles, preformed fibrils, P301S tau, PS19 mice, tau aggregation, microtubule-binding repeats, thioflavin S, proteinase K resistance, transgenic mouse model
- MeSH terms
- Alzheimer Disease, Animals, Brain, Disease Models, Animal, Mice, Transgenic, Phosphorylation, Neurofibrillary Tangles, tau Proteins, Tauopathies, Mice
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
