{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:29:54Z","timestamp":1790692194672,"version":"4.1.0"},"reference-count":179,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T00:00:00Z","timestamp":1623024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tauopathies are a heterogeneous class of neurodegenerative diseases characterized by intracellular inclusions of aggregated tau proteins. Tau aggregates in different tauopathies have distinct structural features and can be found in different cell types. Transgenic animal models overexpressing human tau have been used for over two decades in the research of tau pathology. However, these models poorly recapitulate the heterogeneity of tauopathies found in human brains. Recent findings demonstrate that injection of purified tau aggregates from the brains of human tauopathy patients recapitulates both the structural features and cell-type specificity of the tau pathology of the donor tauopathy. These models may therefore have unique translational value in the study of functional consequences of tau pathology, tau-based diagnostics, and tau targeting therapeutics. This review provides an update of the literature relating to seeding-based tauopathy and their potential applications.<\/jats:p>","DOI":"10.3390\/ijms22116132","type":"journal-article","created":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T13:25:43Z","timestamp":1623072343000},"page":"6132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Tau Seeding Mouse Models with Patient Brain-Derived Aggregates"],"prefix":"10.3390","volume":"22","author":[{"given":"Aiko","family":"Robert","sequence":"first","affiliation":[{"name":"Department of Neurodegenerative Disease, UCL Queen Square, Institute of Neurology, University College London, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sch\u00f6ll","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, UCL Queen Square, Institute of Neurology, University College London, London WC1N 3BG, UK"},{"name":"Wallenberg Centre for Molecular and Translational Medicine and the Department of Psychiatry and Neurochemistry, University of Gothenburg, 413 45 Gothenburg, Sweden"},{"name":"Department of Psychiatry and Neurochemistry, University of Gothenburg, 413 45 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Vogels","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, UCL Queen Square, Institute of Neurology, University College London, London WC1N 3BG, UK"},{"name":"Department of Psychiatry and Neurochemistry, University of Gothenburg, 413 45 Gothenburg, Sweden"},{"name":"Sylics (Synaptologics B.V.), 3721 MA Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Scheltens, P., de Strooper, B., Kivipelto, M., Holstege, H., Ch\u00e9telat, G., Teunissen, C.E., Cummings, J., and van der Flier, W.M. (2021). Alzheimer\u2019s Disease. Lancet.","DOI":"10.1016\/S0140-6736(20)32205-4"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.biopsych.2019.09.019","article-title":"Propagation of Tau Pathology: Integrating Insights from Postmortem and In Vivo Studies","volume":"87","author":"Vogels","year":"2020","journal-title":"Biol. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1212\/WNL.42.3.631","article-title":"Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer\u2019s disease","volume":"42","author":"Arriagada","year":"1992","journal-title":"Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1093\/brain\/awx243","article-title":"Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer\u2019s disease","volume":"140","author":"Bejanin","year":"2017","journal-title":"Brain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e601","DOI":"10.1212\/WNL.0000000000006875","article-title":"Associations between tau, A\u03b2, and cortical thickness with cognition in Alzheimer disease","volume":"92","author":"Ossenkoppele","year":"2019","journal-title":"Neurology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s13195-019-0518-8","article-title":"Tau and atrophy: Domain-specific relationships with cognition","volume":"11","author":"Digma","year":"2019","journal-title":"Alzheimer Res. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.neuron.2016.01.028","article-title":"PET Imaging of Tau Deposition in the Aging Human Brain","volume":"89","author":"Lockhart","year":"2016","journal-title":"Neuron"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1038\/s41467-020-15701-2","article-title":"Spread of pathological tau proteins through communicating neurons in human Alzheimer\u2019s disease","volume":"11","author":"Vogel","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3389\/fnins.2017.00167","article-title":"Tau pathology distribution in Alzheimer\u2019s disease corresponds differentially to cognition-relevant functional brain networks","volume":"11","author":"Hansson","year":"2017","journal-title":"Front. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/ncb1901","article-title":"Transmission and spreading of tauopathy in transgenic mouse brain","volume":"11","author":"Clavaguera","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"12845","DOI":"10.1074\/jbc.M808759200","article-title":"Propagation of Tau misfolding from the outside to the inside of a cell","volume":"284","author":"Frost","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Liu, L., Drouet, V., Wu, J.W., Witter, M.P., Small, S.A., Clelland, C., and Duff, K. (2012). Trans-synaptic spread of tau pathology in vivo. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031302"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.neuron.2011.11.033","article-title":"Propagation of Tau Pathology in a Model of Early Alzheimer\u2019s Disease","volume":"73","author":"Polydoro","year":"2012","journal-title":"Neuron"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1126\/science.1113694","article-title":"Tau Suppression in a Neurodegenerative Mouse Model Improves Memory Function","volume":"309","author":"Santacruz","year":"2005","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.neuron.2007.01.010","article-title":"Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model","volume":"53","author":"Yoshiyama","year":"2007","journal-title":"Neuron"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00401-007-0291-9","article-title":"Tauopathy models and human neuropathology: Similarities and differences","volume":"115","author":"Frank","year":"2008","journal-title":"Acta Neuropathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.neurol.2018.07.001","article-title":"New classification of tauopathies","volume":"174","author":"Respondek","year":"2018","journal-title":"Rev. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/bs.mcb.2017.06.009","article-title":"The use of mouse models to study cell-to-cell transmission of pathological tau","volume":"141","author":"Narasimhan","year":"2017","journal-title":"Methods Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41467-019-13787-x","article-title":"Transmission of tauopathy strains is independent of their isoform composition","volume":"11","author":"He","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9535","DOI":"10.1073\/pnas.1301175110","article-title":"Brain homogenates from human tauopathies induce tau inclusions in mouse brain","volume":"110","author":"Clavaguera","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00401-014-1373-0","article-title":"Differential induction and spread of tau pathology in young PS19 tau transgenic mice following intracerebral injections of pathological tau from Alzheimer\u2019s disease or corticobasal degeneration brains","volume":"129","author":"Boluda","year":"2015","journal-title":"Acta Neuropathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e12179","DOI":"10.1002\/trc2.12179","article-title":"Alzheimer\u2019s Disease Drug Development Pipeline: 2021","volume":"7","author":"Cummings","year":"2021","journal-title":"Alzheimer Dement. Transl. Res. Clin. Interv."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1126\/science.3122323","article-title":"The Primary Structure and Heterogeneity of Tau Protein from Mouse Brain","volume":"239","author":"Lee","year":"1988","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1002\/j.1460-2075.1989.tb03390.x","article-title":"Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem repeats: Differential expression of tau protein mRNAs in human brain","volume":"8","author":"Goedert","year":"1989","journal-title":"EMBO J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10626","DOI":"10.1021\/bi00158a027","article-title":"Structure and Novel Exons of the Human tau Gene","volume":"31","author":"Andreadis","year":"1992","journal-title":"Biochemistry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/nrn.2015.1","article-title":"Tau in physiology and pathology","volume":"17","author":"Wang","year":"2016","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00401-017-1707-9","article-title":"Roles of tau protein in health and disease","volume":"133","author":"Guo","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8597","DOI":"10.1021\/bi3010818","article-title":"FTDP-17 tau mutations induce distinct effects on aggregation and microtubule interactions","volume":"51","author":"Combs","year":"2012","journal-title":"Biochemistry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1074\/jbc.M114.589309","article-title":"Conformation determines the seeding potencies of native and recombinant Tau aggregates","volume":"290","author":"Falcon","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1038\/s41374-019-0197-x","article-title":"MAPT mutations, tauopathy, and mechanisms of neurodegeneration","volume":"99","author":"Strang","year":"2019","journal-title":"Lab. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1093\/hmg\/ddh138","article-title":"The structure of the tau haplotype in controls and in progressive supranuclear palsy","volume":"13","author":"Pittman","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.nbd.2006.10.018","article-title":"The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing transcripts","volume":"25","author":"Myers","year":"2007","journal-title":"Neurobiol. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13024-015-0025-8","article-title":"Regulation of human MAPT gene expression","volume":"10","author":"Sergeant","year":"2015","journal-title":"Mol. Neurodegener."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7247","DOI":"10.1038\/ncomms8247","article-title":"Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy","volume":"6","author":"Kouri","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1001\/jamaneurol.2019.0250","article-title":"Association of mapt subhaplotypes with risk of progressive supranuclear palsy and severity of tau pathology","volume":"76","author":"Heckman","year":"2019","journal-title":"JAMA Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.ajpath.2013.04.025","article-title":"Acetylated tau neuropathology in sporadic and hereditary tauopathies","volume":"183","author":"Irwin","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1042\/BJ20140372","article-title":"Lysine methylation is an endogenous post-translational modification of tau protein in human brain and a modulator of aggregation propensity","volume":"462","author":"Funk","year":"2014","journal-title":"Biochem. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1038\/nm.3951","article-title":"Critical role of acetylation in tau-mediated neurodegeneration and cognitive deficits","volume":"21","author":"Min","year":"2015","journal-title":"Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1046\/j.1471-4159.2003.02287.x","article-title":"Pseudophosphorylation of tau protein alters its ability for self-aggregation","volume":"88","author":"Haase","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"15277","DOI":"10.1074\/jbc.M117.794602","article-title":"An Acetylation\u2013phosphorylation switch that regulates tau aggregation propensity and function","volume":"292","author":"Carlomagno","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1111\/j.1471-4159.2008.05564.x","article-title":"Histone deacetylase 6 interacts with the microtubule-associated protein tau","volume":"106","author":"Ding","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1097\/NEN.0b013e3181922348","article-title":"Sirtuin 1 Reduction Parallels the Accumulation of Tau in Alzheimer Disease","volume":"68","author":"Julien","year":"2009","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3680","DOI":"10.1523\/JNEUROSCI.2369-17.2018","article-title":"iSIRT1 deacetylates tau and reduces pathogenic tau spread in a mouse model of tauopathy","volume":"38","author":"Min","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3582","DOI":"10.1016\/j.febslet.2006.05.029","article-title":"Truncated tau from sporadic Alzheimer\u2019s disease suffices to drive neurofibrillary degeneration in vivo","volume":"580","author":"Zilka","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1097\/NEN.0b013e31823557fb","article-title":"Truncation of tau at E391 Promotes Early Pathologic Changes in Transgenic Mice","volume":"70","author":"McMillan","year":"2011","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"831","DOI":"10.3233\/JAD-160347","article-title":"Human Truncated Tau Induces Mature Neurofibrillary Pathology in a Mouse Model of Human Tauopathy","volume":"54","author":"Zimova","year":"2016","journal-title":"J. Alzheimer Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1038\/mp.2015.228","article-title":"Co-expression of truncated and full-length tau induces severe neurotoxicity","volume":"21","author":"Ozcelik","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.nbd.2015.12.006","article-title":"Caspase-cleaved tau exhibits rapid memory impairment associated with tau oligomers in a transgenic mouse model","volume":"87","author":"Kim","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5129","DOI":"10.1073\/pnas.97.10.5129","article-title":"Assembly of protein into Alzheimer paired helical filaments depends on a local sequence motif (306 VQIVYK 311) forming structure","volume":"97","author":"Friedhoff","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"48165","DOI":"10.1074\/jbc.M105196200","article-title":"Mutations of Tau Protein in Frontotemporal Dementia Promote Aggregation of Paired Helical Filaments by Enhancing Local \u03b2-Structure","volume":"276","author":"Barghorn","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8490","DOI":"10.1038\/ncomms9490","article-title":"Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer\u2019s disease brain","volume":"6","author":"Takeda","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e36584","DOI":"10.7554\/eLife.36584","article-title":"Inert and seed-competent tau monomers suggest structural origins of aggregation","volume":"7","author":"Mirbaha","year":"2018","journal-title":"eLife"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological Stageing of Alzheimer-related Changes","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1093\/brain\/awx171","article-title":"Distinct 18F-AV-1451 tau PET retention patterns in early- and late-onset Alzheimer\u2019s disease","volume":"140","author":"Ossenkoppele","year":"2017","journal-title":"Brain"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1093\/brain\/aww041","article-title":"Distinct tau PET imaging patterns in typical and atypical Alzheimer\u2019s disease","volume":"139","author":"Sarazin","year":"2016","journal-title":"Brain"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1097\/WAD.0000000000000196","article-title":"Tau-PET Binding Distinguishes Patients With Early-stage Posterior Cortical Atrophy From Amnestic Alzheimer Disease Dementia","volume":"31","author":"Day","year":"2017","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Vogel, J.W., Young, A.L., Oxtoby, N.P., Smith, R., Ossenkoppele, R., Strandberg, O.T., La Joie, R., Aksman, L.M., Grothe, M.J., and Iturria-Medina, Y. (2021). Four distinct trajectories of tau deposition identified in Alzheimer\u2019s disease. Nat. Med., 871\u2013881.","DOI":"10.1038\/s41591-021-01309-6"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"eabd1327","DOI":"10.1126\/sciadv.abd1327","article-title":"Patient-centered connectivity-based prediction of tau pathology spread in Alzheimer\u2019s disease","volume":"6","author":"Franzmeier","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s40478-021-01127-4","article-title":"Alzheimer\u2019s disease brain contains tau fractions with differential prion-like activities","volume":"9","author":"Li","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/embor.2013.15","article-title":"Physiological release of endogenous tau is stimulated by neuronal activity","volume":"14","author":"Pooler","year":"2013","journal-title":"EMBO Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1084\/jem.20131685","article-title":"Neuronal activity regulates extracellular tau in vivo","volume":"211","author":"Yamada","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1038\/nn.4328","article-title":"Neuronal activity enhances tau propagation and tau pathology in vivo","volume":"19","author":"Wu","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s40478-016-0386-4","article-title":"Tunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological Tau protein assemblies","volume":"4","author":"Tardivel","year":"2016","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1016\/j.celrep.2018.04.056","article-title":"Unconventional Secretion Mediates the Trans-cellular Spreading of Tau","volume":"23","author":"Katsinelos","year":"2018","journal-title":"Cell Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1016\/j.celrep.2018.10.078","article-title":"Secretion of Tau via an Unconventional Non-vesicular Mechanism","volume":"25","author":"Merezhko","year":"2018","journal-title":"Cell Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.nbd.2012.05.021","article-title":"Constitutive secretion of tau protein by an unconventional mechanism","volume":"48","author":"Chai","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1074\/jbc.M112.394528","article-title":"Small misfolded tau species are internalized via bulk endocytosis and anterogradely and retrogradely transported in neurons","volume":"288","author":"Wu","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"E3138","DOI":"10.1073\/pnas.1301440110","article-title":"Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds","volume":"110","author":"Holmes","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"6382","DOI":"10.1038\/s41598-018-24904-z","article-title":"Tau Internalization is Regulated by 6-O Sulfation on Heparan Sulfate Proteoglycans (HSPGs)","volume":"8","author":"Rauch","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Evans, L.D., Strano, A., Campbell, A., Karakoc, E., Iorio, F., Bassett, A.R., and Livesey, F.J. (2020). Whole genome CRISPR screens identify LRRK2-regulated endocytosis as a major mechanism for extracellular tau uptake by human neurons. bioRxiv.","DOI":"10.1101\/2020.08.11.246363"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"100715","DOI":"10.1016\/j.jbc.2021.100715","article-title":"Regulation of tau internalization, degradation, and seeding by LRP1 reveals multiple pathways for tau catabolism","volume":"296","author":"Cooper","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"403","DOI":"10.3389\/fncel.2019.00403","article-title":"Normal and Pathological Tau Uptake Mediated by M1\/M3 Muscarinic Receptors Promotes Opposite Neuronal Changes","volume":"13","author":"Morozova","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/s41586-020-2156-5","article-title":"LRP1 is a master regulator of tau uptake and spread","volume":"580","author":"Rauch","year":"2020","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/j.celrep.2016.09.063","article-title":"Loss of Bin1 Promotes the Propagation of Tau Pathology","volume":"17","author":"Calafate","year":"2016","journal-title":"Cell Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1007\/s00401-017-1722-x","article-title":"Endocytic vesicle rupture is a conserved mechanism of cellular invasion by amyloid proteins","volume":"134","author":"Flavin","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1016\/j.cell.2020.10.029","article-title":"Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer\u2019s Disease","volume":"183","author":"Wesseling","year":"2020","journal-title":"Cell"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Moloney, C.M., Lowe, V.J., and Murray, M.E. (2021). Visualization of neurofibrillary tangle maturity in Alzheimer\u2019s disease: A clinicopathologic perspective for biomarker research. Alzheimer Dement.","DOI":"10.1002\/alz.12321"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s00401-018-1914-z","article-title":"Tau filaments from multiple cases of sporadic and inherited Alzheimer\u2019s disease adopt a common fold","volume":"136","author":"Falcon","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41586-020-2043-0","article-title":"Novel tau filament fold in corticobasal degeneration","volume":"580","author":"Zhang","year":"2020","journal-title":"Nature"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/s41586-019-1026-5","article-title":"Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules","volume":"568","author":"Falcon","year":"2019","journal-title":"Nature"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s00401-021-02294-3","article-title":"Cryo-EM structures of tau filaments from Alzheimer\u2019s disease with PET ligand APN-1607","volume":"141","author":"Shi","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.sbi.2020.05.011","article-title":"Cryo-EM structures of tau filaments","volume":"64","author":"Scheres","year":"2020","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nature23002","article-title":"Cryo-EM structures of tau filaments from Alzheimer\u2019s disease","volume":"547","author":"Fitzpatrick","year":"2017","journal-title":"Nature"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41583-018-0054-8","article-title":"Rodent models for Alzheimer disease","volume":"19","author":"Bodea","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1046\/j.1471-4159.2003.01879.x","article-title":"Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms","volume":"86","author":"Andorfer","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/978-981-32-9358-8_28","article-title":"Experimental Models of Tauopathy\u2013From Mechanisms to Therapies","volume":"1184","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"31755","DOI":"10.1074\/jbc.M705282200","article-title":"The \u03b2-propensity of tau determines aggregation and synaptic loss in inducible mouse models of tauopathy","volume":"282","author":"Eckermann","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"530","DOI":"10.15252\/embr.201541438","article-title":"Expression of A152T human tau causes age-dependent neuronal dysfunction and loss in transgenic mice","volume":"17","author":"Maeda","year":"2016","journal-title":"EMBO Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1093\/brain\/aww137","article-title":"Tauopathy induced by low level expression of a human brain-derived tau fragment in mice is rescued by phenylbutyrate","volume":"139","author":"Bondulich","year":"2016","journal-title":"Brain"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/78078","article-title":"Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein","volume":"25","author":"Lewis","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3539","DOI":"10.1523\/JNEUROSCI.0081-05.2005","article-title":"Transgenic mouse model of tau pathology in astrocytes leading to nervous system degeneration","volume":"25","author":"Forman","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"9434","DOI":"10.1523\/JNEUROSCI.2691-05.2005","article-title":"Axonal degeneration induced by targeted expression of mutant human tau in oligodendrocytes of transgenic mice that model glial tauopathies","volume":"25","author":"Higuchi","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1523\/JNEUROSCI.3861-05.2006","article-title":"Impaired glutamate transport in a mouse model of tau pathology in astrocytes","volume":"26","author":"Forman","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1038\/s41467-019-10428-1","article-title":"Factors other than hTau overexpression that contribute to tauopathy-like phenotype in rTg4510 mice","volume":"10","author":"Gamache","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s41593-019-0560-7","article-title":"Microglial microRNAs mediate sex-specific responses to tau pathology","volume":"23","author":"Kodama","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Harris, J.A., Koyama, A., Maeda, S., Ho, K., Devidze, N., Dubal, D.B., Yu, G.-Q., Masliah, E., and Mucke, L. (2012). Human P301L-Mutant Tau Expression in Mouse Entorhinal-Hippocampal Network Causes Tau Aggregation and Presynaptic Pathology but No Cognitive Deficits. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045881"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1038\/nn.4132","article-title":"Depletion of microglia and inhibition of exosome synthesis halt tau propagation","volume":"18","author":"Asai","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.15252\/embj.201592748","article-title":"Removing endogenous tau does not prevent tau propagation yet reduces its neurotoxicity","volume":"34","author":"Wegmann","year":"2015","journal-title":"EMBO J."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1038\/s41593-020-00728-x","article-title":"Tau accumulation in astrocytes of the dentate gyrus induces neuronal dysfunction and memory deficits in Alzheimer\u2019s disease","volume":"23","author":"Richetin","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1093\/brain\/awab011","article-title":"Neuronal tau species transfer to astrocytes and induce their loss according to tau aggregation state","volume":"144","author":"Augustin","year":"2021","journal-title":"Brain"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4388","DOI":"10.1038\/s41467-018-06783-0","article-title":"APOE \u03b52 is associated with increased tau pathology in primary tauopathy","volume":"9","author":"Zhao","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_102","unstructured":"Rodrigues, S., Anglada-Huguet, M., Hochgr\u00e4fe, K., Kaniyappan, S., Wegmann, S., and Mandelkow, E.-M. (2021, May 05). Spreading of Tau Protein Does Not Depend on Aggregation Propensity. Available online: https:\/\/assets.researchsquare.com\/files\/rs-356350\/v1\/36b64d6c-8143-4d1b-8afe-282465fea9e3.pdf."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1038\/s41467-021-22501-9","article-title":"Acetylated tau inhibits chaperone-mediated autophagy and promotes tau pathology propagation in mice","volume":"12","author":"Caballero","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"eaaw6404","DOI":"10.1126\/sciadv.aaw6404","article-title":"Experimental evidence for the age dependence of tau protein spread in the brain","volume":"5","author":"Wegmann","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"551","DOI":"10.3233\/JAD-200047","article-title":"Viral Delivery of Non-Mutated Human Truncated Tau to Neurons Recapitulates Key Features of Human Tauopathy in Wild-Type Mice","volume":"77","author":"Vogels","year":"2020","journal-title":"J. Alzheimer Dis."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/s00401-014-1254-6","article-title":"A novel in vivo model of tau propagation with rapid and progressive neurofibrillary tangle pathology: The pattern of spread is determined by connectivity, not proximity","volume":"127","author":"Ahmed","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1523\/JNEUROSCI.2642-12.2013","article-title":"Synthetic tau fibrils mediate transmission of neurofibrillary tangles in a transgenic mouse model of alzheimer\u2019s-like tauopathy","volume":"33","author":"Iba","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.nbd.2014.08.032","article-title":"Intracerebral injection of preformed synthetic tau fibrils initiates widespread tauopathy and neuronal loss in the brains of tau transgenic mice","volume":"73","author":"Peeraer","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"11485","DOI":"10.1523\/JNEUROSCI.2393-17.2017","article-title":"GFP-mutant human tau transgenic mice develop tauopathy following CNS injections of Alzheimer\u2019s brain-derived pathological tau or synthetic mutant human tau fibrils","volume":"37","author":"Gibbons","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1084\/jem.20160833","article-title":"Unique pathological tau conformers from alzheimer\u2019s brains transmit tau pathology in nontransgenic mice","volume":"213","author":"Guo","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e43584","DOI":"10.7554\/eLife.43584","article-title":"Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer\u2019s and Pick\u2019s diseases","volume":"8","author":"Zhang","year":"2019","journal-title":"eLife"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"12754","DOI":"10.1074\/jbc.RA119.009487","article-title":"Humanization of the entire murine Mapt gene provides a murine model of pathological human tau propagation","volume":"294","author":"Saito","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/nm.4443","article-title":"Amyloid-\u03b2 plaques enhance Alzheimer\u2019s brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation","volume":"24","author":"He","year":"2018","journal-title":"Nat. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/s41593-019-0433-0","article-title":"TREM2 function impedes tau seeding in neuritic plaques","volume":"22","author":"Leyns","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s00401-018-1953-5","article-title":"Amyloid-\u03b2 pathology enhances pathological fibrillary tau seeding induced by Alzheimer PHF in vivo","volume":"137","author":"Vergara","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s40478-019-0725-3","article-title":"Cerebrospinal fluid from Alzheimer\u2019s disease patients promotes tau aggregation in transgenic mice","volume":"7","author":"Skachokova","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.3233\/JAD-201002","article-title":"Learning Deficits Accompanied by Microglial Proliferation After the Long-Term Post-Injection of Alzheimer\u2019s Disease Brain Extract in Mouse Brains","volume":"79","author":"Hayashi","year":"2021","journal-title":"J. Alzheimer Dis."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"9933","DOI":"10.1523\/JNEUROSCI.1907-16.2016","article-title":"Calpain activation in Alzheimer\u2019s model mice is an artifact of APP and presenilin overexpression","volume":"36","author":"Saito","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s00401-021-02264-9","article-title":"Photodynamic studies reveal rapid formation and appreciable turnover of tau inclusions","volume":"141","author":"Croft","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/srep00700","article-title":"Alzheimer brain-derived tau oligomers propagate pathology from endogenous tau","volume":"2","author":"Sengupta","year":"2012","journal-title":"Sci. Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1016\/j.ajpath.2016.06.008","article-title":"High\u2013Molecular-Weight Paired Helical Filaments from Alzheimer Brain Induces Seeding of Wild-Type Mouse Tau into an Argyrophilic 4R Tau Pathology in Vivo","volume":"186","author":"Audouard","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"11406","DOI":"10.1523\/JNEUROSCI.1230-17.2017","article-title":"Pathological tau strains from human brains recapitulate the diversity of tauopathies in nontransgenic mouse brain","volume":"37","author":"Narasimhan","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s00401-019-02122-9","article-title":"Familial globular glial tauopathy linked to MAPT mutations: Molecular neuropathology and seeding capacity of a prototypical mixed neuronal and glial tauopathy","volume":"139","author":"Ferrer","year":"2020","journal-title":"Acta Neuropathol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1111\/bpa.12593","article-title":"Aging-related tau astrogliopathy (ARTAG): Not only tau phosphorylation in astrocytes","volume":"28","author":"Ferrer","year":"2018","journal-title":"Brain Pathol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"112","DOI":"10.3389\/fnagi.2019.00112","article-title":"Involvement of oligodendrocytes in tau seeding and spreading in tauopathies","volume":"11","author":"Ferrer","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/bpa.12778","article-title":"Relevance of host tau in tau seeding and spreading in tauopathies","volume":"30","author":"Ferrer","year":"2020","journal-title":"Brain Pathol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3389\/fnmol.2020.00101","article-title":"Capacity for Seeding and Spreading of Argyrophilic Grain Disease in a Wild-Type Murine Model; Comparisons with Primary Age-Related Tauopathy","volume":"13","author":"Ferrer","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3389\/fnagi.2020.00011","article-title":"Differences between Human and Murine Tau at the N-terminal End","volume":"12","author":"Avila","year":"2020","journal-title":"Front. Aging Neurosci."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1111\/neup.12108","article-title":"Pretangles and neurofibrillary changes: Similarities and differences between AD and CBD based on molecular and morphological evolution","volume":"34","author":"Uchihara","year":"2014","journal-title":"Neuropathology"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.jalz.2016.01.014","article-title":"Hyperphosphorylation determines both the spread and the morphology of tau pathology","volume":"12","author":"Hu","year":"2016","journal-title":"Alzheimer Dement."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3389\/fnagi.2019.00034","article-title":"Pathological Tau From Alzheimer\u2019s Brain Induces Site-Specific Hyperphosphorylation and SDS- and Reducing Agent-Resistant Aggregation of Tau in vivo","volume":"11","author":"Miao","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"589471","DOI":"10.3389\/fneur.2020.589471","article-title":"Tau Isoform-Driven CBD Pathology Transmission in Oligodendrocytes in Humanized Tau Mice","volume":"11","author":"Patra","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00401-020-02253-4","article-title":"In vitro amplification of pathogenic tau conserves disease-specific bioactive characteristics","volume":"141","author":"Xu","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1093\/jnen\/nlaa086","article-title":"Insoluble Tau From Human FTDP-17 Cases Exhibit Unique Transmission Properties In Vivo","volume":"79","author":"Weitzman","year":"2020","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"S97","DOI":"10.3233\/JAD-132477","article-title":"Specific targeting of tau oligomers in Htau mice prevents cognitive impairment and tau toxicity following injection with brain-derived tau oligomeric seeds","volume":"40","author":"Gerson","year":"2014","journal-title":"J. Alzheimer Dis."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S0896-6273(03)00434-3","article-title":"Triple-Transgenic Model of Alzheimer\u2019s Disease with Plaques and Tangles: Intracellular A and Synaptic Dysfunction","volume":"39","author":"Oddo","year":"2003","journal-title":"Neuron"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"e12873","DOI":"10.1111\/acel.12873","article-title":"Temporal and regional progression of Alzheimer\u2019s disease-like pathology in 3xTg-AD mice","volume":"18","author":"Belfiore","year":"2019","journal-title":"Aging Cell"},{"key":"ref_138","unstructured":"Lam, S., Boluda, S., H\u00e9rard, A.-S., Petit, F., Eddarkaoui, S., Cambon, K., Picq, J.L., Buee, L., Duyckaerts, C., and Haik, S. (2021). Alzheimer\u2019s brain inoculation in A\u00df-plaque bearing mice: Synaptic loss is linked to tau seeding and low microglial activity. bioRxiv."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3389\/fnmol.2020.00106","article-title":"Intravenous Injection of PHF-Tau Proteins From Alzheimer Brain Exacerbates Neuroinflammation, Amyloid Beta, and Tau Pathologies in 5XFAD Transgenic Mice","volume":"13","author":"Houben","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1038\/s41591-020-0938-9","article-title":"Tau molecular diversity contributes to clinical heterogeneity in Alzheimer\u2019s disease","volume":"26","author":"Dujardin","year":"2020","journal-title":"Nat. Med."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1007\/s00401-019-02046-4","article-title":"Granulovacuolar degeneration bodies are neuron-selective lysosomal structures induced by intracellular tau pathology","volume":"138","author":"Wiersma","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"eaay8826","DOI":"10.1126\/science.aay8826","article-title":"Autosomal dominant VCP hypomorph mutation impairs disaggregation of PHF-tau","volume":"370","author":"Darwich","year":"2020","journal-title":"Science"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"e20190783","DOI":"10.1084\/jem.20190783","article-title":"Human tau pathology transmits glial tau aggregates in the absence of neuronal tau","volume":"217","author":"Narasimhan","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1084\/jem.20172158","article-title":"TFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading","volume":"215","author":"Cole","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"645233","DOI":"10.3389\/fncel.2021.645233","article-title":"Astrocytic Propagation of Tau in the Context of Alzheimer\u2019s Disease","volume":"15","author":"Fleeman","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13024-017-0192-x","article-title":"Glial contributions to neurodegeneration in tauopathies","volume":"12","author":"Leyns","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1056\/NEJMoa1211103","article-title":"Variant of TREM2 Associated with the Risk of Alzheimer\u2019s Disease","volume":"368","author":"Jonsson","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/s41467-018-08279-3","article-title":"Neuropathological correlates and genetic architecture of microglial activation in elderly human brain","volume":"10","author":"Felsky","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1016\/j.neuron.2018.10.014","article-title":"Changes in the Synaptic Proteome in Tauopathy and Rescue of Tau-Induced Synapse Loss by C1q Antibodies","volume":"100","author":"Dejanovic","year":"2018","journal-title":"Neuron"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1016\/j.celrep.2018.07.072","article-title":"Living Neurons with Tau Filaments Aberrantly Expose Phosphatidylserine and Are Phagocytosed by Microglia","volume":"24","author":"Brelstaff","year":"2018","journal-title":"Cell Rep."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s40478-019-0754-y","article-title":"Intersection of pathological tau and microglia at the synapse","volume":"7","author":"Vogels","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1186\/s12974-018-1309-z","article-title":"The role of microglia in processing and spreading of bioactive tau seeds in Alzheimer\u2019s disease","volume":"15","author":"Hopp","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13024-021-00440-9","article-title":"Plaque associated microglia hyper-secrete extracellular vesicles and accelerate tau propagation in a humanized APP mouse model","volume":"16","author":"Clayton","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1056\/NEJMoa1211851","article-title":"TREM2 Variants in Alzheimer\u2019s Disease","volume":"368","author":"Guerreiro","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Wang, C., Fan, L., Zhan, L., Kodama, L., Liu, B., Chin, M.Y., Li, Y., Le, D., Zhou, Y., and Condello, C. (2021). Microglial NF-\u03baB drives tau spreading and toxicity in a mouse model of tauopathy. bioRxiv.","DOI":"10.1101\/2021.02.22.432272"},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Henderson, M.X., Changolkar, L., Trojanowski, J.Q., and Lee, V.M.Y. (2021). LRRK2 Kinase Activity Does Not Alter Cell-Autonomous Tau Pathology Development in Primary Neurons. J. Parkinson Dis.","DOI":"10.3233\/JPD-212562"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Henderson, M.X., Cornblath, E.J., Li, H.L., Changolkar, L., Zhang, B., Brown, H.J., Gathagan, R.J., Olufemi, M.F., Bassett, D.S., and Trojanowski, J.Q. (2020). Tau pathology spreads between anatomically-connected regions of the brain and is modulated by a LRRK2 mutation. bioRxiv.","DOI":"10.1101\/2020.10.13.337857"},{"key":"ref_158","unstructured":"Healy, D.G., Falchi, M., O\u2019sullivan, S.S., Bonifati, V., Durr, A., Bressman, S., Brice, A., Aasly, J., Zabetian, C.P., and Goldwurm, S. (2021, April 12). Phenotype, Genotype, and Worldwide Genetic Penetrance of LRRK2-Associated Parkinson\u2019s Disease: A Case-Control Study. Available online: http:\/\/neurology.thelancet.com."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"214.e1","DOI":"10.1016\/j.neurobiolaging.2018.11.007","article-title":"Genetic analysis of neurodegenerative diseases in a pathology cohort","volume":"76","author":"Blauwendraat","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1186\/s40478-019-0836-x","article-title":"Alzheimer\u2019s disease tau is a prominent pathology in LRRK2 Parkinson\u2019s disease","volume":"7","author":"Henderson","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/ana.25392","article-title":"Cognitive and Pathological Influences of Tau Pathology in Lewy Body Disorders","volume":"85","author":"Coughlin","year":"2019","journal-title":"Ann. Neurol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0022-510X(99)00327-5","article-title":"Occurrence of human a-synuclein immunoreactive neurons with neurofibrillary tangle formation in the limbic areas of patients with Alzheimer\u2019s disease","volume":"174","author":"Marui","year":"2000","journal-title":"J. Neurol. Sci."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0006-8993(00)03082-1","article-title":"\u03b1-Synuclein-positive structures in cases with sporadic Alzheimer\u2019s disease: Morphology and its relationship to tau aggregation","volume":"888","author":"Arai","year":"2001","journal-title":"Brain Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"e20192193","DOI":"10.1084\/jem.20192193","article-title":"\u03b1-Synuclein modulates tau spreading in mouse brains","volume":"218","author":"Bassil","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.cell.2013.05.057","article-title":"Distinct \u03b1-Synuclein Strains Differentially Promote Tau Inclusions in Neurons","volume":"154","author":"Guo","year":"2013","journal-title":"Cell"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"265","DOI":"10.3233\/JAD-180404","article-title":"Anti-tau monoclonal antibodies derived from soluble and filamentous tau show diverse functional properties in vitro and in vivo","volume":"65","author":"Vandermeeren","year":"2018","journal-title":"J. Alzheimer Dis."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s00401-018-1911-2","article-title":"Epitope determines efficacy of therapeutic anti-Tau antibodies in a functional assay with human Alzheimer Tau","volume":"136","author":"Courade","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1016\/j.ajpath.2017.01.022","article-title":"Tau Antibody Targeting Pathological Species Blocks Neuronal Uptake and Interneuron Propagation of Tau in Vitro","volume":"187","author":"Nobuhara","year":"2017","journal-title":"Am. J. Pathol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.trci.2018.09.005","article-title":"Highly specific and selective anti-pS396-tau antibody C10.2 targets seeding-competent tau","volume":"4","author":"Rosenqvist","year":"2018","journal-title":"Alzheimer Dement. Transl. Res. Clin. Interv."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s00702-014-1315-y","article-title":"Passive immunization targeting the N-terminal projection domain of tau decreases tau pathology and improves cognition in a transgenic mouse model of Alzheimer disease and tauopathies","volume":"122","author":"Dai","year":"2015","journal-title":"J. Neural Transm."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13195-018-0341-7","article-title":"Tau passive immunization blocks seeding and spread of Alzheimer hyperphosphorylated Tau-induced pathology in 3 \u00d7 Tg-AD mice","volume":"10","author":"Dai","year":"2018","journal-title":"Alzheimer Res. Ther."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1093\/brain\/awz100","article-title":"Prevention of tau seeding and propagation by immunotherapy with a central tau epitope antibody","volume":"142","author":"Albert","year":"2019","journal-title":"Brain"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13024-020-00404-5","article-title":"Conformation-selective tau monoclonal antibodies inhibit tau pathology in primary neurons and a mouse model of Alzheimer\u2019s disease","volume":"15","author":"Gibbons","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3389\/fnins.2018.00267","article-title":"Synaptic tau seeding precedes tau pathology in human Alzheimer\u2019s disease brain","volume":"12","author":"DeVos","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"5143","DOI":"10.1038\/sj.emboj.7601917","article-title":"Hyperphosphorylated tau in parahippocampal cortex impairs place learning in aged mice expressing wild-type human tau","volume":"26","author":"Kimura","year":"2007","journal-title":"EMBO J."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s40478-021-01141-6","article-title":"Tau assemblies do not behave like independently acting prion-like particles in mouse neural tissue","volume":"9","author":"Miller","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.bpc.2018.07.005","article-title":"Conformational heterogeneity of tau: Implication on intrinsic disorder, acid stability and fibrillation in Alzheimer\u2019s disease","volume":"241","author":"Jebarupa","year":"2018","journal-title":"Biophys. Chem."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"343","DOI":"10.3389\/fnagi.2019.00343","article-title":"Genetic Background Influences the Propagation of Tau Pathology in Transgenic Rodent Models of Tauopathy","volume":"11","author":"Smolek","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s12035-018-1102-0","article-title":"First-in-Rat Study of Human Alzheimer\u2019s Disease Tau Propagation","volume":"56","author":"Smolek","year":"2019","journal-title":"Mol. Neurobiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/6132\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:11:33Z","timestamp":1760163093000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/6132"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,7]]},"references-count":179,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["ijms22116132"],"URL":"https:\/\/doi.org\/10.3390\/ijms22116132","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,7]]}}}