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As a novel tau PET tracer in AD, [\n                    <jats:sup>18<\/jats:sup>\n                    F]MK-6240 has the potential in Down syndrome-associated Alzheimer\u2019s disease (DSAD) to elucidate pathophysiology and advance diagnostic strategies. Autoradiography of frontal cortex and temporal cortex postmortem brain slices of DSAD (n\u2009=\u20095), AD (n\u2009=\u20095), and cognitively normal (CN) (n\u2009=\u20095) cases indicated similarly high [\n                    <jats:sup>18<\/jats:sup>\n                    F]MK-6240 binding in DSAD and AD cases. [\n                    <jats:sup>18<\/jats:sup>\n                    F]MK-6240 binding in CN was substantially less than DSAD and AD. Anti-tau immunostains confirmed total tau presence that aligned with the localization of [\n                    <jats:sup>18<\/jats:sup>\n                    F]MK-6240 binding. DSAD and AD cases exhibited higher gray matter (GM)\/white matter ratios of 2.8 and 2.5 respectively. For drug effects on [\n                    <jats:sup>18<\/jats:sup>\n                    F]MK-6240 binding, self-displacement by MK-6240 (10\u00a0\u00b5M) reduced binding by 88% among DSAD cases and 85% among AD cases while IPPI (10\u00a0\u00b5M) displaced [\n                    <jats:sup>18<\/jats:sup>\n                    F]MK-6240 by 81% and 74% in DSAD and AD cases respectively. KuFal194 (10\u00a0\u00b5M), a specific phosphokinase inhibitor, minimally displaced [\n                    <jats:sup>18<\/jats:sup>\n                    F]MK-6240 binding. Harmine competed with [\n                    <jats:sup>18<\/jats:sup>\n                    F]MK-6240 with an IC\n                    <jats:sub>50<\/jats:sub>\n                    value of 290\u00a0nM and 92\u00a0nM for DSAD and AD cases, respectively. High meninges off-target (non-tau) binding of [\n                    <jats:sup>18<\/jats:sup>\n                    F]MK-6240 was observed in a CN case, comparable to the GM in DSAD and AD. MK-6240 (10\u00a0\u00b5M) blocked 44% and T807 (10\u00a0\u00b5M) blocked 30% of meninges binding. Incubation of meninges in the presence of 0.2% polyethyleneimine reduced 70% of [\n                    <jats:sup>18<\/jats:sup>\n                    F]MK-6240 binding. The tau radioligand, [\n                    <jats:sup>125<\/jats:sup>\n                    I]IPPI, an analog of [\n                    <jats:sup>18<\/jats:sup>\n                    F]MK-6240, exhibited minimal binding to CN meninges compared to the DSAD and AD cases. Our findings suggest [\n                    <jats:sup>18<\/jats:sup>\n                    F]MK-6240 to be selective tau imaging agent in DSAD and AD, harmine to uniquely compete with [\n                    <jats:sup>18<\/jats:sup>\n                    F]MK-6240 binding in DSAD and provide preliminary insights to the off-target nonspecific binding of [\n                    <jats:sup>18<\/jats:sup>\n                    F]MK-6240 in postmortem meninges.\n                  <\/jats:p>","DOI":"10.1186\/s40478-026-02267-1","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T10:53:11Z","timestamp":1773485591000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of [18F]MK-6240 binding to tau protein in postmortem human brains of Down syndrome and Alzheimer\u2019s disease and assessment of off-target (non-tau) binding"],"prefix":"10.1186","volume":"14","author":[{"given":"Fariha","family":"Karim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes P.","family":"Biju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camryn J.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maharishi","family":"Rajarethenam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jogeshwar","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,14]]},"reference":[{"issue":"5","key":"2267_CR1","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1111\/j.1365-2788.2010.01271.x","volume":"54","author":"D Adams","year":"2010","unstructured":"Adams D, Oliver C (2010) The relationship between acquired impairments of executive function and behaviour change in adults with Down syndrome. 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