{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:33:15Z","timestamp":1785429195237,"version":"3.56.0"},"posted":{"date-parts":[[2026,1,21]]},"group-title":"Neuroscience","reference-count":43,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"award":["AG077700"],"award-info":[{"award-number":["AG077700"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The accumulation of tau tangles and A\u03b2 plaques are prominent neuropathologies that characterize Alzheimer\u2019s disease (AD) and Down Syndrome (DS). Continuous developments of PET tracers as biomarkers can be supported by autoradiography to validate effectiveness and accuracy of binding properties that elucidate the pathophysiology of DSAD and AD. This in vitro comparative study evaluates [\n                  <jats:sup>125<\/jats:sup>\n                  I]IPPI binding to tau and [\n                  <jats:sup>125<\/jats:sup>\n                  I]IBETA binding to A\u03b2 plaques in the frontal cortex (FCX) and temporal cortex (TCX) of postmortem human brain slices of AD (n=5), DSAD (n=5), and cognitively normal (CN) (n=5) cases. With anti-tau and anti-A\u03b2 immunostains confirming the presence of tau and A\u03b2 plaques, [\n                  <jats:sup>125<\/jats:sup>\n                  I]IPPI and [\n                  <jats:sup>125<\/jats:sup>\n                  I]IBETA binding in autoradiographic images were significantly higher in DSAD and AD gray matter (GM) compared to CN. When comparing DSAD with AD, FCX and TCX GM binding was similar throughout DSAD and AD except in FCX GM where there was 48% more [\n                  <jats:sup>125<\/jats:sup>\n                  I]IPPI binding in DSAD than AD. In vitro drug inhibition studies revealed that [\n                  <jats:sup>125<\/jats:sup>\n                  I]IPPI binding was significantly inhibited with increasing harmine concentrations (IC\n                  <jats:sub>50<\/jats:sub>\n                  =115\u00b140 nM) in DSAD FCX and TCX but KuFal194 minimally inhibited [\n                  <jats:sup>125<\/jats:sup>\n                  I]IPPI binding in the same cases. The GM\/white matter ratios for DSAD ([\n                  <jats:sup>125<\/jats:sup>\n                  I]IPPI=4.1, [\n                  <jats:sup>125<\/jats:sup>\n                  I]IBETA=2.9) and AD ([\n                  <jats:sup>125<\/jats:sup>\n                  I]IPPI=4.2, [\n                  <jats:sup>125<\/jats:sup>\n                  I]IBETA=2.6) were significantly greater than CN ([\n                  <jats:sup>125<\/jats:sup>\n                  I]IPPI=1.3, [\n                  <jats:sup>125<\/jats:sup>\n                  I]IBETA=1.2). A positive correlation between [\n                  <jats:sup>125<\/jats:sup>\n                  I]IPPI and [\n                  <jats:sup>125<\/jats:sup>\n                  I]IBETA binding suggests a synergistic relationship between tau and A\u03b2 plaque in DSAD and AD pathology. This study demonstrates that [\n                  <jats:sup>125<\/jats:sup>\n                  I]IPPI and [\n                  <jats:sup>125<\/jats:sup>\n                  I]IBETA may serve as novel radiotracers in both DSAD and AD to continue diagnostic investigations in vivo.\n                <\/jats:p>","DOI":"10.64898\/2026.01.17.700075","type":"posted-content","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T23:50:11Z","timestamp":1769039411000},"source":"Crossref","is-referenced-by-count":0,"title":["Measurement of tau protein and A\u03b2 amyloid plaques in postmortem human brains of Down syndrome and Alzheimer\u2019s disease by using [\n                  <sup>125<\/sup>\n                  I]IPPI and [\n                  <sup>125<\/sup>\n                  I]IBETA autoradiography"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0267-2299","authenticated-orcid":false,"given":"Agnes 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