{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T09:58:41Z","timestamp":1785232721993,"version":"3.55.0"},"reference-count":45,"publisher":"The Company of Biologists","issue":"7","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000320","name":"Alzheimer's Society","doi-asserted-by":"crossref","award":["574"],"award-info":[{"award-number":["574"]}],"id":[{"id":"10.13039\/501100000320","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003547","name":"Bangor University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003547","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Tauopathies are characterised by progressive deterioration of brain regions due to abnormal accumulation of microtubule-associated protein tau (MAPT). Alternative splicing of MAPT pre-mRNA produces six isoforms, classified as 3R or 4R depending on whether they contain three or four microtubule-binding repeats. Although many tauopathies are 3R or 4R specific, individual isoform contributions to neurotoxicity remain unclear. To investigate isoform-specific toxicity, we generated Drosophila lines with transgenes encoding each human tau (hTau) isoform inserted at the same locus. In young adults, hTau abundance did not differ significantly among lines, yet expression levels were sufficient to induce visible, isoform-specific phenotypes. Across assays, hTau toxicity depended on expression window, tissue type, and neuronal identity; 4R isoforms were generally more toxic than 3R isoforms, but individual isoform effects differed by context. In selected neuronal populations, neurons classed as vulnerable showed early degeneration and continued decline, whereas resilient neurons degenerated only at the later time point. This suggests that, in some neurons, resilience may reflect early resistance to disease processes that is lost with age and exposure to age-related stressors. These phenotypes were not readily explained by hTau abundance or AT8-positive hTau. Together, we show that tau toxicity emerges from interactions between isoform-specific properties and cellular environment.<\/jats:p>","DOI":"10.1242\/bio.062644","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T14:47:51Z","timestamp":1783522071000},"source":"Crossref","is-referenced-by-count":0,"title":["Context-dependent toxicity of human tau isoforms in a\n                    <i>Drosophila<\/i>\n                    tauopathy model"],"prefix":"10.1242","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4054-8716","authenticated-orcid":false,"given":"Yelena","family":"Ivanova","sequence":"first","affiliation":[{"name":"School of Environmental and Natural Sciences, Bangor University 1 , Bangor LL57 2UR ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1559-8976","authenticated-orcid":false,"given":"Miguel","family":"Ramirez-Moreno","sequence":"additional","affiliation":[{"name":"Centre for Biological Sciences, University of Southampton 2 , Southampton SO17 1BJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1144-3830","authenticated-orcid":false,"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"University of British Columbia 3 Department of Cellular and Physiological Sciences , , Vancouver V6T 1Z3 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3672-3705","authenticated-orcid":false,"given":"Leila","family":"Abtahi","sequence":"additional","affiliation":[{"name":"University of British Columbia 3 Department of Cellular and Physiological Sciences , , Vancouver V6T 1Z3 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1080-864X","authenticated-orcid":false,"given":"Baidong","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Computer Sciences and Engineering, Bangor University 4 , Bangor LL57 1UT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2525-0148","authenticated-orcid":false,"given":"Amber S.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Centre for Biological Sciences, University of Southampton 2 , Southampton SO17 1BJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3282-1052","authenticated-orcid":false,"given":"Zengbo","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Computer Sciences and Engineering, Bangor University 4 , Bangor LL57 1UT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3488-8365","authenticated-orcid":false,"given":"Douglas W.","family":"Allan","sequence":"additional","affiliation":[{"name":"University of British Columbia 3 Department of Cellular and Physiological Sciences , , Vancouver V6T 1Z3 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0880-1107","authenticated-orcid":false,"given":"Amritpal","family":"Mudher","sequence":"additional","affiliation":[{"name":"Centre for Biological Sciences, University of Southampton 2 , Southampton SO17 1BJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3954-2416","authenticated-orcid":false,"given":"Aaron A.","family":"Comeault","sequence":"additional","affiliation":[{"name":"School of Environmental and Natural Sciences, Bangor University 1 , Bangor LL57 2UR ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5160-2697","authenticated-orcid":false,"given":"Lovesha","family":"Sivanatharajah","sequence":"additional","affiliation":[{"name":"School of Environmental and Natural Sciences, Bangor University 1 , Bangor LL57 2UR ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"2026072805010655800_BIO062644C1","doi-asserted-by":"publisher","first-page":"2504","DOI":"10.3791\/2504","article-title":"Assaying locomotor, learning, and memory deficits in Drosophila models of neurodegeneration","volume":"49","author":"Ali","year":"2011","journal-title":"J. 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