{"doi":"10.1002/syn.70024","title":"[<sup>125</sup>I]IPPI for Tau Imaging: Binding Studies in Postmortem Human Alzheimer's Disease Hippocampus‐Subiculum and Evaluation of Drug Effects","abstract":"ABSTRACT 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 [ 125 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‐A), and dual specificity tyrosine‐phosphorylation regulated kinase 1A (DYRK1A). Quantitative [ 125 I]IPPI binding was compared between AD ( n = 29; 13 male and 16 female) and cognitively normal (CN) ( n = 32; 16 male and 16 female) subjects. Significantly, there was more [ 125 I]IPPI binding in AD gray matter (GM), which positively correlated with the percent of anti‐tau immunostaining. GM/white matter (WM) ratios in AD were higher compared to CN subjects. Female AD (avg. GM/WM = 2.42) exhibited greater [ 125 I]IPPI binding compared to males (avg. GM/WM = 1.91). Binding of [ 125 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 [ 125 I]IPPI binding to tau and [ 18 F]flotaza binding to amyloid beta (Aβ) suggests potential pathophysiological associations between the two AD biomarkers. MK‐6240 (aggregated tau‐selective) and harmine (MAO‐A, DYRK1A, and tau nonselective) inhibited [ 125 I]IPPI binding by 88% and 69%, respectively. No effect on [ 125 I]IPPI binding was observed by selective DYRK1A (KuFal194) and MAO‐A (clorgyline) inhibitors. Affinity of harmine for tau binding sites was quantified by inhibitor concentration (IC 50 ) = 135 ± 29 nM. This study demonstrates promise of radiolabeled IPPI as a viable and selective tau radiotracer to assist in the diagnostic imaging of AD in humans.","journal":"Synapse","year":2025,"id":514808,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9588,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1065145,"name":"Brooke A. Delaney","orcid":null,"position":1,"is_corresponding":false},{"id":1049092,"name":"Rommani Mondal","orcid":null,"position":2,"is_corresponding":false},{"id":725634,"name":"Christopher Liang","orcid":"0000-0001-9081-294X","position":3,"is_corresponding":false},{"id":256002,"name":"Geidy E. Serrano","orcid":"0000-0002-9527-2011","position":4,"is_corresponding":false},{"id":107088,"name":"Thomas G. Beach","orcid":"0000-0003-3296-6128","position":5,"is_corresponding":false},{"id":579729,"name":"Jogeshwar Mukherjee","orcid":"0000-0003-1009-877X","position":6,"is_corresponding":false},{"id":1248871,"name":"Fariha Karim","orcid":"0009-0001-3104-9523","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:48:34.431522Z","pmid":"40619690","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}