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Here, we report the methods for the development of sensitive biosensor cell lines for the detection of tau seeding activity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We performed the rational design of novel tau probes based on the current structural knowledge of pathological tau aggregates in Alzheimer\u2019s disease. We generated F\u00f6rster resonance energy transfer (FRET)-based biosensor stable cell lines and characterized their sensitivity, specificity, and overall ability to detect bioactive tau in human samples. As compared to the reference biosensor line, the optimized probe design resulted in an increased efficiency in the detection of tau seeding. The increased sensitivity allowed for the detection of lower amount of tau seeding competency in human brain samples, while preserving specificity for tau seeds found in Alzheimer\u2019s disease.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This next generation of FRET-based biosensor cells is a novel tool to study tau seeding activity in Alzheimer\u2019s disease human samples, especially in samples with low levels of seeding activity, which may help studying early tau-related pathological events.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13024-023-00643-2","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T07:02:29Z","timestamp":1691478149000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Specific detection of tau seeding activity in Alzheimer\u2019s disease using rationally designed biosensor cells"],"prefix":"10.1186","volume":"18","author":[{"given":"Aurelien","family":"Lathuiliere","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youhwa","family":"Jo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Perbet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Donahue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Commins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00e9","family":"Quittot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanyun","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel E.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7959-9401","authenticated-orcid":false,"given":"Bradley T.","family":"Hyman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"643_CR1","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1038\/emboj.2013.207","volume":"32","author":"H Zempel","year":"2013","unstructured":"Zempel H, Luedtke J, Kumar Y, Biernat J, Dawson H, Mandelkow E, Mandelkow EM. 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He serves on a scientific advisory board or is a consultant for AbbVie, Aprinoia Therapeutics, Arvinas, Avrobio, Axial, Biogen, BMS, Cure Alz Fund, Cell Signaling, Eisai, Genentech, Ionis, Latus, Novartis, Sangamo, Sanofi, Seer, Takeda, the US Dept of Justice, Vigil, Voyager. His laboratory is supported by research grants from the National Institutes of Health, Cure Alzheimer\u2019s Fund, Tau Consortium, and the JPB Foundation \u2013 and sponsored research agreements from Abbvie, BMS, and Biogen.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"53"}}