{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T17:03:37Z","timestamp":1770829417810,"version":"3.50.1"},"reference-count":109,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cLa Caixa\u201d Foundation","award":["HR18-00452"],"award-info":[{"award-number":["HR18-00452"]}]},{"name":"\u201cLa Caixa\u201d Foundation","award":["Intra-CIBERNED 2019"],"award-info":[{"award-number":["Intra-CIBERNED 2019"]}]},{"name":"CERCA Programme\/Generalitat de Catalunya","award":["HR18-00452"],"award-info":[{"award-number":["HR18-00452"]}]},{"name":"CERCA Programme\/Generalitat de Catalunya","award":["Intra-CIBERNED 2019"],"award-info":[{"award-number":["Intra-CIBERNED 2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Heterozygous hTau mice were used for the study of tau seeding. These mice express the six human tau isoforms, with a high predominance of 3Rtau over 4Rtau. The following groups were assessed: (i) non-inoculated mice aged 9 months (n = 4); (ii) Alzheimer\u2019s Disease (AD)-inoculated mice (n = 4); (iii) Globular Glial Tauopathy (GGT)-inoculated mice (n = 4); (iv) Pick\u2019s disease (PiD)-inoculated mice (n = 4); (v) control-inoculated mice (n = 4); and (vi) inoculated with vehicle alone (n = 2). AD-inoculated mice showed AT8-immunoreactive neuronal pre-tangles, granular aggregates, and dots in the CA1 region of the hippocampus, dentate gyrus (DG), and hilus, and threads and dots in the ipsilateral corpus callosum. GGT-inoculated mice showed unique or multiple AT8-immunoreactive globular deposits in neurons, occasionally extended to the proximal dendrites. PiD-inoculated mice showed a few loose pre-tangles in the CA1 region, DG, and cerebral cortex near the injection site. Coiled bodies were formed in the corpus callosum in AD-inoculated mice, but GGT-inoculated mice lacked globular glial inclusions. Tau deposits in inoculated mice co-localized active kinases p38-P and SAPK\/JNK-P, thus suggesting active phosphorylation of the host tau. Tau deposits were absent in hTau mice inoculated with control homogenates and vehicle alone. Deposits in AD-inoculated hTau mice contained 3Rtau and 4Rtau; those in GGT-inoculated mice were mainly stained with anti-4Rtau antibodies, but a small number of deposits contained 3Rtau. Deposits in PiD-inoculated mice were stained with anti-3Rtau antibodies, but rare neuronal, thread-like, and dot-like deposits showed 4Rtau immunoreactivity. These findings show that tau strains produce different patterns of active neuronal seeding, which also depend on the host tau. Unexpected 3Rtau and 4Rtau deposits after inoculation of homogenates from 4R and 3R tauopathies, respectively, suggests the regulation of exon 10 splicing of the host tau during the process of seeding, thus modulating the plasticity of the cytoskeleton.<\/jats:p>","DOI":"10.3390\/ijms232415940","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T01:52:30Z","timestamp":1671069150000},"page":"15940","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Common and Specific Marks of Different Tau Strains Following Intra-Hippocampal Injection of AD, PiD, and GGT Inoculum in hTau Transgenic Mice"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9888-8754","authenticated-orcid":false,"given":"Isidro","family":"Ferrer","sequence":"first","affiliation":[{"name":"Department of Pathology and Experimental Therapeutics, University of Barcelona, 08907 L\u2019Hospitalet de Llobregat, Barcelona, Spain"},{"name":"Neuropathology Group, Institute of Biomedical Research (IDIBELL), 08907 L\u2019Hospitalet de Llobregat, Barcelona, Spain"},{"name":"Network Centre of Biomedical Research of Neurodegenerative Diseases (CIBERNED), Institute of Health Carlos III, 08907 L\u2019Hospitalet de Llobregat, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pol","family":"Andr\u00e9s-Benito","sequence":"additional","affiliation":[{"name":"Neuropathology Group, Institute of Biomedical Research (IDIBELL), 08907 L\u2019Hospitalet de Llobregat, Barcelona, Spain"},{"name":"Network Centre of Biomedical Research of Neurodegenerative Diseases (CIBERNED), Institute of Health Carlos III, 08907 L\u2019Hospitalet de Llobregat, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margarita","family":"Carmona","sequence":"additional","affiliation":[{"name":"Neuropathology Group, Institute of Biomedical Research (IDIBELL), 08907 L\u2019Hospitalet de Llobregat, Barcelona, Spain"},{"name":"Network Centre of Biomedical Research of Neurodegenerative Diseases (CIBERNED), Institute of Health Carlos III, 08907 L\u2019Hospitalet de Llobregat, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5214-4909","authenticated-orcid":false,"given":"Jos\u00e9 Antonio","family":"del Rio","sequence":"additional","affiliation":[{"name":"Network Centre of Biomedical Research of Neurodegenerative Diseases (CIBERNED), Institute of Health Carlos III, 08907 L\u2019Hospitalet de Llobregat, Barcelona, Spain"},{"name":"Molecular and Cellular Neurobiotechnology Group, Institute of Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology, Science Park Barcelona (PCB), 08028 Barcelona, Barcelona, Spain"},{"name":"Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, 08028 Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"ref_1","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_2","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_3","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_4","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_5","doi-asserted-by":"crossref","unstructured":"Dujardin, S., B\u00e9gard, S., Caillierez, R., Lachaud, C., Delattre, L., Carrier, S., Loyens, A., Galas, M.-C., Bousset, L., and Melki, R. (2014). Ectosomes: A new mechanism for non-exosomal secretion of tau protein. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100760"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/2051-5960-2-14","article-title":"Neuron-to-neuron wild-type Tau protein transfer through a trans-synaptic mechanism: Relevance to sporadic tauopathies","volume":"2","author":"Dujardin","year":"2014","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s40478-018-0514-4","article-title":"Exosomes taken up by neurons hijack the endosomal pathway to spread to interconnected neurons","volume":"6","author":"Polanco","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/978-981-32-9358-8_11","article-title":"Tau secretion","volume":"1184","author":"Ruan","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_11","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_12","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_13","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13024-016-0143-y","article-title":"The release and trans-synaptic transmission of tau via exosomes","volume":"12","author":"Wang","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_14","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_15","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_16","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_17","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_18","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_19","first-page":"909","article-title":"Transmission and spreading of tauopathy in transgenic mouse brain","volume":"11","author":"Clavaguera","year":"2009","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"15317","DOI":"10.1074\/jbc.M110.209296","article-title":"Seeding of normal Tau by pathological Tau conformers drives pathogenesis of Alzheimer-like tangles","volume":"286","author":"Guo","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"19440","DOI":"10.1074\/jbc.M112.346072","article-title":"Trans-cellular propagation of tau aggregation by fibrillar species","volume":"287","author":"Kfoury","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"3842","DOI":"10.1074\/jbc.M111.277061","article-title":"Exosome-associated Tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease","volume":"287","author":"Saman","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_24","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_25","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_26","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_27","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_28","doi-asserted-by":"crossref","first-page":"E8187","DOI":"10.1073\/pnas.1616344113","article-title":"Tau prions from Alzheimer\u2019s disease and chronic traumatic encephalopathy patients propagate in cultured cells","volume":"113","author":"Woerman","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s00401-015-1507-z","article-title":"Propagation of tau pathology: Hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies","volume":"131","author":"Lewis","year":"2015","journal-title":"Acta Neuropathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1146\/annurev-neuro-072116-031153","article-title":"Propagation of tau aggregates and neurodegeneration","volume":"40","author":"Goedert","year":"2017","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13041-017-0298-7","article-title":"Propagation of Tau aggregates","volume":"10","author":"Goedert","year":"2017","journal-title":"Mol. Brain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/s40478-017-0488-7","article-title":"What is the evidence that tau pathology spreads through prion-like propagation?","volume":"5","author":"Mudher","year":"2017","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Guix, F.X., Corbett, G.T., Cha, D.J., Mustapic, M., Liu, W., Mengel, D., Chen, Z., Aikawa, E., Young-Pearse, T., and Kapogiannis, D. (2018). Detection of aggregation-competent tau in neuron-derived extracellular vesicles. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030663"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1007\/s11481-017-9768-z","article-title":"Extracellular vesicle biology in Alzheimer\u2019s disease and related tauopathy","volume":"13","author":"DeLeo","year":"2017","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1001\/jamaneurol.2018.2505","article-title":"Mechanisms of cell-to-cell transmission of pathological tau","volume":"76","author":"Gibbons","year":"2019","journal-title":"JAMA Neurol."},{"key":"ref_36","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_37","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_38","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_39","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\u2019s Dement."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9340","DOI":"10.1523\/JNEUROSCI.22-21-09340.2002","article-title":"Abundant tau filaments and non-apoptotic neurodegeneration in transgenic mice expressing human P301S tau protein","volume":"22","author":"Allen","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_41","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_42","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_43","doi-asserted-by":"crossref","unstructured":"Takeuchi, H., Iba, M., Inoue, H., Higuchi, M., Takao, K., Tsukita, K., Karatsu, Y., Iwamoto, Y., Miyakawa, T., and Suhara, T. (2011). P301S mutant human tau transgenic mice manifest early symptoms of human tauopathies with dementia and altered sen-sorimotor gating. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021050"},{"key":"ref_44","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_45","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/978-981-32-9358-8_28","article-title":"Experimental models of tauopathy\u2014From mechanisms to therapies","volume":"1184","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_46","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_47","doi-asserted-by":"crossref","unstructured":"Robert, A., Sch\u00f6ll, M., and Vogels, T. (2021). Tau seeding mouse models with patient brain-derived aggregates. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116132"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1093\/brain\/awab289","article-title":"Development of a novel tau propagation mouse model endogenously expressing 3 and 4 repeat tau isoforms","volume":"145","author":"Hosokawa","year":"2021","journal-title":"Brain"},{"key":"ref_49","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_50","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1111\/bpa.12044","article-title":"\u201cPrion-like\u201d templated misfolding in tauopathies","volume":"23","author":"Clavaguera","year":"2013","journal-title":"Brain Pathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/nan.12197","article-title":"Invited review: Prion-like transmission and spreading of tau pathology","volume":"41","author":"Clavaguera","year":"2015","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.neuron.2016.09.055","article-title":"Tau prion strains dictate patterns of cell pathology, progression rate, and regional vulnerability in vivo","volume":"92","author":"Kaufman","year":"2016","journal-title":"Neuron"},{"key":"ref_53","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":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_54","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_55","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_56","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_57","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_58","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_59","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_60","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_61","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_62","doi-asserted-by":"crossref","unstructured":"Ferrer, I., Andr\u00e9s-Benito, P., Garcia-Esparcia, P., L\u00f3pez-Gonzalez, I., Valiente, D., Jord\u00e1n-Pirla, M., Carmona, M., Sala-Jarque, J., Gil, V., and del Rio, J.A. (2022). Differences in Tau Seeding in Newborn and Adult Wild-Type Mice. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094789"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/j.neuron.2014.04.047","article-title":"Distinct tau prion strains propagate in cells and mice and define different tauopathies","volume":"82","author":"Sanders","year":"2014","journal-title":"Neuron"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Andr\u00e9s-Benito, P., Carmona, M., Jord\u00e1n, M., Fern\u00e1ndez-Irigoyen, J., Santamar\u00eda, E., del Rio, J.A., and Ferrer, I. (2022). Host tau genotype specifically designs and regulates tau seeding and spreading and host tau transformation following intrahippocampal injection of identical tau ad inoculum. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020718"},{"key":"ref_65","unstructured":"Paxinos, G., and Franklin, K.B.J. (2019). The Mouse Brain in Stereotaxic Coordinates, Elsevier. [5th ed.]."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0079-6123(08)64310-1","article-title":"Chapter 17 Neuronal cytoskeleton in aging and dementia","volume":"70","author":"Iqbal","year":"1986","journal-title":"Prog. Brain Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4051","DOI":"10.1073\/pnas.85.11.4051","article-title":"Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: Identification as microtubule-associated protein tau","volume":"85","author":"Goedert","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/0896-6273(88)90129-8","article-title":"Epitopes that span the tau molecule are shared with paired helical filaments","volume":"1","author":"Kosik","year":"1988","journal-title":"Neuron"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1097\/00005072-199602000-00004","article-title":"Specific pathological tau protein variants characterize Pick\u2019s disease","volume":"55","author":"Delacourte","year":"1996","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/ana.410430209","article-title":"Vulnerable neuronal subsets in Alzheimer\u2019s and Pick\u2019s disease are distinguished by their \u03c4 isoform distribution and phosphorylation","volume":"43","author":"Delacourte","year":"1998","journal-title":"Ann. Neurol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/0896-6273(92)90117-V","article-title":"Tau proteins of alzheimer paired helical filaments: Abnormal phosphorylation of all six brain isoforms","volume":"8","author":"Goedert","year":"1992","journal-title":"Neuron"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1111\/j.1750-3639.1999.tb00550.x","article-title":"Comparative biochemistry of tau in progressive supranuclear palsy, corticobasal degeneration, FTDP-17 and Pick\u2019s disease","volume":"9","author":"Delacourte","year":"1999","journal-title":"Brain Pathol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1212\/WNL.52.6.1158","article-title":"The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer\u2019s disease","volume":"52","author":"Delacourte","year":"1999","journal-title":"Neurology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s004010000283","article-title":"Distinct isoforms of tau aggregated in neurons and glial cells in brains of patients with Pick\u2019s disease, corticobasal degeneration and progressive supranuclear palsy","volume":"101","author":"Arai","year":"2001","journal-title":"Acta Neuropathol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/j.1440-1789.2006.00743.x","article-title":"Cellular tau pathology and immunohistochemical study of tau isoforms in sporadic tauopathies","volume":"26","author":"Yoshida","year":"2006","journal-title":"Neuropathology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s00401-011-0857-4","article-title":"Globular glial tauopathies (GGT) presenting with motor neuron disease or frontotemporal dementia: An emerging group of 4-repeat tauopathies","volume":"122","author":"Ahmed","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"a006247","DOI":"10.1101\/cshperspect.a006247","article-title":"Biochemistry and cell biology of tau protein in neurofibrillary degeneration","volume":"2","author":"Mandelkow","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1097\/NEN.0000000000000030","article-title":"Glial and neuronal tau pathology in tauopathies: Characterization of disease-specific phenotypes and tau pathology progression","volume":"73","author":"Ferrer","year":"2014","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/978-981-32-9358-8_2","article-title":"Structure of NFT: Biochemical approach","volume":"1184","author":"Hasegawa","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"581936","DOI":"10.3389\/fnins.2020.581936","article-title":"Comparison of common and disease-specific post-translational modifications of pathological tau associated with a wide range of tauopathies","volume":"14","author":"Kametani","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_81","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_82","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41586-018-0454-y","article-title":"Structures of filaments from Pick\u2019s disease reveal a novel tau protein fold","volume":"561","author":"Falcon","year":"2018","journal-title":"Nature"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41586-021-03911-7","article-title":"Structure-based classification of tauopathies","volume":"598","author":"Shi","year":"2021","journal-title":"Nature"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13024-021-00476-x","article-title":"Cellular and pathological heterogeneity of primary tauopathies","volume":"16","author":"Chung","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/bs.pmbts.2020.08.003","article-title":"Tau proteinopathies and the prion concept","volume":"175","author":"Goedert","year":"2020","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s00401-021-02301-7","article-title":"Tau strains shape disease","volume":"142","author":"Diamond","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s00401-022-02426-3","article-title":"Ultrastructural and biochemical classification of pathogenic tau, \u03b1-synuclein and TDP-43","volume":"143","author":"Tarutani","year":"2022","journal-title":"Acta Neuropathol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Han, Z.Z., Kang, S.-G., Arce, L., and Westaway, D. (2022). Prion-like strain effects in tauopathies. Cell Tissue Res.","DOI":"10.1007\/s00441-022-03620-1"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s40478-019-0691-9","article-title":"Tau exhibits unique seeding properties in globular glial tauopathy","volume":"7","author":"Chung","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1002\/ana.10222","article-title":"Sporadic Pick\u2019s disease: A tauopathy characterized by a spectrum of pathological tau isoforms in gray and white matter","volume":"51","author":"Zhukareva","year":"2002","journal-title":"Ann. Neurol."},{"key":"ref_91","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":"2019","journal-title":"Brain Pathol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1093\/brain\/awab091","article-title":"Human tauopathy-derived tau strains determine the substrates recruited for templated amplification","volume":"144","author":"Tarutani","year":"2021","journal-title":"Brain"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s00401-022-02425-4","article-title":"Unique seeding profiles and prion-like propagation of synucleinopathies are highly dependent on the host in human \u03b1-synuclein transgenic mice","volume":"143","author":"Lloyd","year":"2022","journal-title":"Acta Neuropathol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1002\/glia.23865","article-title":"Focal cerebral ischemia induces changes in oligodendrocytic tau isoforms in the damaged area","volume":"68","author":"Avila","year":"2020","journal-title":"Glia"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4225","DOI":"10.1002\/j.1460-2075.1990.tb07870.x","article-title":"Expression of separate isoforms of human tau protein: Correlation with the tau pattern in brain and effects on tubulin polymerization","volume":"9","author":"Goedert","year":"1990","journal-title":"EMBO J."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0165-3806(03)00056-7","article-title":"Isoforms changes of tau protein during development in various species","volume":"142","author":"Takuma","year":"2003","journal-title":"Dev. Brain Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.bbadis.2004.08.010","article-title":"Tau gene alternative splicing: Expression patterns, regulation and modulation of function in normal brain and neurodegenerative diseases","volume":"1739","author":"Andreadis","year":"2005","journal-title":"Biochim. Et Biophys. Acta BBA Mol. Basis Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"56","DOI":"10.2174\/1874609810801010056","article-title":"Tau as a molecular marker of development, aging and neurodegenerative disorders","volume":"1","author":"Avila","year":"2008","journal-title":"Curr. Aging Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s12264-013-1411-2","article-title":"Regulation of alternative splicing of tau exon 10","volume":"30","author":"Qian","year":"2014","journal-title":"Neurosci. Bull."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Hefti, M.M., Farrell, K., Kim, S., Bowles, K.R., Fowkes, M.E., Raj, T., and Crary, J.F. (2018). High-resolution temporal and regional mapping of MAPT expression and splicing in human brain development. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0195771"},{"key":"ref_101","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_102","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":"Buee","year":"2015","journal-title":"Mol. Neurodegener."},{"key":"ref_103","first-page":"57","article-title":"Brain pathology in myotonic dystrophy: When tauopathy meets spliceopathy and RNAopathy","volume":"6","author":"Dhaenens","year":"2014","journal-title":"Front. Mol. Neurosci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"539","DOI":"10.2174\/1389450115666140226112321","article-title":"Human CDC2-like kinase 1 (CLK1): A novel target for Alzheimer\u2019s disease","volume":"15","author":"Jain","year":"2014","journal-title":"Curr. Drug Targets"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/S1474-4422(13)70090-5","article-title":"Tau pathology and neurodegeneration","volume":"12","author":"Spillantini","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"9548","DOI":"10.1073\/pnas.1633508100","article-title":"Differential regulation of microtubule dynamics by three- and four-repeat tau: Implications for the onset of neurodegenerative disease","volume":"100","author":"Panda","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_107","first-page":"467","article-title":"Brain banking","volume":"Volume 1","author":"Aminoff","year":"2014","journal-title":"Encyclopedia of the Neurological Sciences"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1111\/j.1365-2990.2012.01272.x","article-title":"Neuropathology of the hippocampus in FTLD-Tau with Pick bodies: A study of the BrainNet Europe Consortium","volume":"39","author":"Kovacs","year":"2012","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"5446","DOI":"10.1523\/JNEUROSCI.4637-04.2005","article-title":"Cell-cycle reentry and cell death in transgenic mice expressing nonmutant human tau isoforms","volume":"25","author":"Andorfer","year":"2005","journal-title":"J. Neurosci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15940\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:41:32Z","timestamp":1760146892000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15940"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,14]]},"references-count":109,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232415940"],"URL":"https:\/\/doi.org\/10.3390\/ijms232415940","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,14]]}}}