{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T17:56:14Z","timestamp":1773770174028,"version":"3.50.1"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,6]],"date-time":"2025-07-06T00:00:00Z","timestamp":1751760000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG077700"],"award-info":[{"award-number":["AG077700"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Synapse"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Alzheimer's disease (AD) is characterized by the accumulation of tau tangles that aggregate into neurofibrillary tangles (NFT). This study aims to assess binding of [<jats:sup>125<\/jats:sup>I]IPPI, a recently reported imaging probe for pathological, aggregated tau in AD human hippocampus (HP) postmortem brain slices, and measure effects of drugs known to bind to tau, monoamine oxidase A (MAO\u2010A), and dual specificity tyrosine\u2010phosphorylation regulated kinase 1A (DYRK1A). Quantitative [<jats:sup>125<\/jats:sup>I]IPPI binding was compared between AD (<jats:italic>n<\/jats:italic>\u00a0=\u00a029; 13 male and 16 female) and cognitively normal (CN) (<jats:italic>n<\/jats:italic>\u00a0=\u00a032; 16 male and 16 female) subjects. Significantly, there was more [<jats:sup>125<\/jats:sup>I]IPPI binding in AD gray matter (GM), which positively correlated with the percent of anti\u2010tau immunostaining. GM\/white matter (WM) ratios in AD were higher compared to CN subjects. Female AD (avg. GM\/WM\u00a0=\u00a02.42) exhibited greater [<jats:sup>125<\/jats:sup>I]IPPI binding compared to males (avg. GM\/WM\u00a0=\u00a01.91). Binding of [<jats:sup>125<\/jats:sup>I]IPPI increased with Braak neurofibrillary stages of the subjects, and the effects of aging were mixed, with females showing a downward trend. A positive correlation between [<jats:sup>125<\/jats:sup>I]IPPI binding to tau and [<jats:sup>18<\/jats:sup>F]flotaza binding to amyloid beta (A\u03b2) suggests potential pathophysiological associations between the two AD biomarkers. MK\u20106240 (aggregated tau\u2010selective) and harmine (MAO\u2010A, DYRK1A, and tau nonselective) inhibited [<jats:sup>125<\/jats:sup>I]IPPI binding by 88% and 69%, respectively. No effect on [<jats:sup>125<\/jats:sup>I]IPPI binding was observed by selective DYRK1A (KuFal194) and MAO\u2010A (clorgyline) inhibitors. Affinity of harmine for tau binding sites was quantified by inhibitor concentration (IC<jats:sub>50<\/jats:sub>)\u00a0=\u00a0135\u00a0\u00b1\u00a029\u00a0nM. This study demonstrates promise of radiolabeled IPPI as a viable and selective tau radiotracer to assist in the diagnostic imaging of AD in humans.<\/jats:p>","DOI":"10.1002\/syn.70024","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:56:47Z","timestamp":1751849807000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["[<sup>125<\/sup>I]IPPI for Tau Imaging: Binding Studies in Postmortem Human Alzheimer's Disease Hippocampus\u2010Subiculum and Evaluation of Drug Effects"],"prefix":"10.1002","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3104-9523","authenticated-orcid":false,"given":"Fariha","family":"Karim","sequence":"first","affiliation":[{"name":"Department of Radiological Sciences, Preclinical Imaging University of California\u2010Irvine  Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brooke A.","family":"Delaney","sequence":"additional","affiliation":[{"name":"Department of Radiological Sciences, Preclinical Imaging University of California\u2010Irvine  Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rommani","family":"Mondal","sequence":"additional","affiliation":[{"name":"Department of Radiological Sciences, Preclinical Imaging University of California\u2010Irvine  Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Radiological Sciences, Preclinical Imaging University of California\u2010Irvine  Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geidy E.","family":"Serrano","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute  Sun City Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas G.","family":"Beach","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute  Sun City Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1009-877X","authenticated-orcid":false,"given":"Jogeshwar","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Radiological Sciences, Preclinical Imaging University of California\u2010Irvine  Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010023\u201002672\u2010z"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010019\u20100686\u20106"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000065892.67099.2A"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/neup.12189"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264\u2010013\u20101414\u2010z"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx347"},{"key":"e_1_2_9_9_1","first-page":"458","article-title":"Sex Differences in Alzheimer's Disease\u2010 the Gateway to Precision Medicine","volume":"14","author":"Ferretti M. 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