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Here, we performed a large-scale seroepidemiological search for anti-tau IgG autoantibodies (\u03b1\u03c4) on 40,497 human plasma samples. High-titer \u03b1\u03c4\n                    <jats:sup>+<\/jats:sup>\n                    individuals were surprisingly prevalent, with hospital patients being three times more likely to be \u03b1\u03c4\n                    <jats:sup>+<\/jats:sup>\n                    (EC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009\u2265\u20092\n                    <jats:sup>6<\/jats:sup>\n                    ; a nominal dilution of &gt;1\/64) than healthy blood donors (4.8% versus 1.6%). The prevalence increased with age over 70 years-old (RR 1.26, 95% CI 1.11\u20131.43,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001) and was higher for women (RR 1.20, 95% CI 1.07\u20131.39,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.002). The autoantibodies bound selectively to tau, inhibited tau aggregation in vitro, and interfered with tau detection in plasma samples. No association was found between \u03b1\u03c4 autoantibodies and neurological disorders. Instead, tau autoreactivity showed a significant association with kidney and urinary disorders (adjusted RR 1.27, 95% CI 1.10\u20131.45,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.001 and 1.40, 95% CI 1.20\u20131.63,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001, respectively). These results suggest a previously unrecognized association between \u03b1\u03c4 autoimmunity and extraneural diseases.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3003488","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T18:41:22Z","timestamp":1764182482000},"page":"e3003488","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Large-scale seroepidemiology uncovers nephro-urological pathologies in people with tau autoimmunity"],"prefix":"10.1371","volume":"23","author":[{"given":"Andreia D.","family":"Magalh\u00e3es","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Emmenegger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"De Cecco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfredi","family":"Carta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Frontzek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andra","family":"Chincisan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2674-9891","authenticated-orcid":true,"given":"Simone","family":"Hornemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0344-6708","authenticated-orcid":true,"given":"Adriano","family":"Aguzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"issue":"3","key":"pbio.3003488.ref001","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1046\/j.1471-4159.1996.67031235.x","article-title":"Tau is widely expressed in rat tissues","volume":"67","author":"Y Gu","year":"1996","journal-title":"J Neurochem"},{"issue":"6220","key":"pbio.3003488.ref002","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. 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