{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T01:38:39Z","timestamp":1789695519781,"version":"4.0.1"},"reference-count":50,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T00:00:00Z","timestamp":1641772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"La Caixa Banking Foundation","award":["HR18-00452"],"award-info":[{"award-number":["HR18-00452"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Several studies have demonstrated the different characteristics of tau seeding and spreading following intracerebral inoculation in murine models of tau-enriched fractions of brain homogenates from AD and other tauopathies. The present study is centered on the importance of host tau in tau seeding and the molecular changes associated with the transformation of host tau into abnormal tau. The brains of three adult murine genotypes expressing different forms of tau\u2014WT (murine 4Rtau), hTau (homozygous transgenic mice knock-out for murine tau protein and heterozygous expressing human forms of 3Rtau and 4Rtau proteins), and mtWT (homozygous transgenic mice knock-out for murine tau protein)\u2014were analyzed following unilateral hippocampal inoculation of sarkosyl-insoluble tau fractions from the same AD and control cases. The present study reveals that (a) host tau is mandatory for tau seeding and spreading following tau inoculation from sarkosyl-insoluble fractions obtained from AD brains; (b) tau seeding does not occur following intracerebral inoculation of sarkosyl-insoluble fractions from controls; (c) tau seeding and spreading are characterized by variable genotype-dependent tau phosphorylation and tau nitration, MAP2 phosphorylation, and variable activation of kinases that co-localize with abnormal tau deposits; (d) transformation of host tau into abnormal tau is an active process associated with the activation of specific kinases; (e) tau seeding is accompanied by modifications in tau splicing, resulting in the expression of new 3Rtau and 4Rtau isoforms, thus indicating that inoculated tau seeds have the capacity to model exon 10 splicing of the host mapt or MAPT with a genotype-dependent pattern; (e) selective regional and cellular vulnerabilities, and different molecular compositions of the deposits, are dependent on the host tau of mice injected with identical AD tau inocula.<\/jats:p>","DOI":"10.3390\/ijms23020718","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T17:42:25Z","timestamp":1641836545000},"page":"718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Host Tau Genotype Specifically Designs and Regulates Tau Seeding and Spreading and Host Tau Transformation Following Intrahippocampal Injection of Identical Tau AD Inoculum"],"prefix":"10.3390","volume":"23","author":[{"given":"Pol","family":"Andr\u00e9s-Benito","sequence":"first","affiliation":[{"name":"Neuropathology Group, Institute of Biomedical Research, IDIBELL, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"CIBERNED (Network Centre of Biomedical Research of Neurodegenerative Diseases), Institute of Health Carlos III, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Carmona","sequence":"additional","affiliation":[{"name":"Neuropathology Group, Institute of Biomedical Research, IDIBELL, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"CIBERNED (Network Centre of Biomedical Research of Neurodegenerative Diseases), Institute of Health Carlos III, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Jord\u00e1n","sequence":"additional","affiliation":[{"name":"CIBERNED (Network Centre of Biomedical Research of Neurodegenerative Diseases), Institute of Health Carlos III, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5072-4099","authenticated-orcid":false,"given":"Joaqu\u00edn","family":"Fern\u00e1ndez-Irigoyen","sequence":"additional","affiliation":[{"name":"Clinical Neuroproteomics Unit, Proteomics Platform, Proteored-ISCIII, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad P\u00fablica de Navarra (UPNA), diSNA, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8046-8102","authenticated-orcid":false,"given":"Enrique","family":"Santamar\u00eda","sequence":"additional","affiliation":[{"name":"Clinical Neuroproteomics Unit, Proteomics Platform, Proteored-ISCIII, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad P\u00fablica de Navarra (UPNA), diSNA, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5214-4909","authenticated-orcid":false,"given":"Jos\u00e9 Antoni","family":"del Rio","sequence":"additional","affiliation":[{"name":"CIBERNED (Network Centre of Biomedical Research of Neurodegenerative Diseases), Institute of Health Carlos III, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Science Park Barcelona (PCB), Barcelona Institute for Science and Technology, 08028 Barcelona, Spain"},{"name":"Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9888-8754","authenticated-orcid":false,"given":"Isidro","family":"Ferrer","sequence":"additional","affiliation":[{"name":"Neuropathology Group, Institute of Biomedical Research, IDIBELL, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"CIBERNED (Network Centre of Biomedical Research of Neurodegenerative Diseases), Institute of Health Carlos III, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Department of Pathology and Experimental Therapeutics, University of Barcelona, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/nan.12208","article-title":"Invited review: Neuropathology of tauopathies: Principles and practice","volume":"41","author":"Kovacs","year":"2015","journal-title":"Neuropathol. 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