{"doi":"10.1002/syn.22265","title":"Abnormal [<sup>18</sup>F]NIFENE binding in transgenic 5xFAD mouse model of Alzheimer's disease: In vivo PET/CT imaging studies of α4β2* nicotinic acetylcholinergic receptors and in vitro correlations with Aβ plaques","abstract":"Abstract Since cholinergic dysfunction has been implicated in Alzheimer's disease (AD), the effects of Aβ plaques on nicotinic acetylcholine receptors (nAChRs) α4β2* subtype were studied using the transgenic 5xFAD mouse model of AD. Using the PET radiotracer [ 18 F]nifene for α4β2* nAChRs, in vitro autoradiography and in vivo PET/CT studies in 5xFAD mice were carried out and compared with wild‐type (C57BL/6) mice. Ratios of [ 18 F]nifene binding in brain regions versus cerebellum (CB) in 5xFAD mice brains were for thalamus (TH) = 17, hippocampus‐subiculum = 7, frontal cortex (FC) = 5.5, and striatum = 4.7. [ 125 I]IBETA and immunohistochemistry (IHC) in 5xFAD brain slices confirmed Aβ plaques. Nicotine and acetylcholine displaced [ 18 F]nifene in 5xFAD mice (IC 50 nicotine = 31–73 nM; ACh = 38–83 nM) and C57BL/6 (IC 50 nicotine = 16–18 nM; ACh = 34–55 nM). Average [ 18 F]nifene SUVR (CB as reference) in 5xFAD mice was significantly higher in FC = 3.04 compared to C57BL/6 mice FC = 1.92 ( p = .001), whereas TH difference between 5xFAD mice (SUVR = 2.58) and C57BL/6 mice (SUVR = 2.38) was not significant. Nicotine‐induced dissociation half life (t 1/2 ) of [ 18 F]nifene for TH were 37 min for 5xFAD mice and 26 min for C57BL/6 mice. Dissociation half life for FC in C57BL/6 mice was 77 min , while no dissociation of [ 18 F]nifene occurred in the medial prefrontal cortex (mFC) of 5xFAD mice. Coregistration of [ 18 F]nifene PET with MR suggested that the mPFC, and anterior cingulate (AC) regions exhibited high uptake in 5xFAD mice compared to C57BL/6 mice. Ex vivo [ 18 F]nifene and in vitro [ 125 I]IBETA Aβ plaque autoradiography after in vivo PET/CT scan of 5xFAD mouse brain were moderately correlated ( r 2 = 0.68). In conclusion, 5xFAD mice showed increased non‐displaceable [ 18 F]nifene binding in mPFC.","journal":"Synapse","year":2023,"id":359012,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1065146,"name":"Grace A. H. Nguyen","orcid":null,"position":1,"is_corresponding":false},{"id":1109679,"name":"Tram B. Danh","orcid":null,"position":2,"is_corresponding":false},{"id":1109680,"name":"Anoopraj K. Sandhu","orcid":null,"position":3,"is_corresponding":false},{"id":1109681,"name":"Lusine L. Melkonyan","orcid":null,"position":4,"is_corresponding":false},{"id":1049091,"name":"Amina U. Syed","orcid":null,"position":5,"is_corresponding":false},{"id":579729,"name":"Jogeshwar Mukherjee","orcid":"0000-0003-1009-877X","position":6,"is_corresponding":false},{"id":725634,"name":"Christopher Liang","orcid":"0000-0001-9081-294X","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T01:13:48.379546Z","pmid":"36749986","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":[]}