{"doi":"10.1016/j.brainres.2025.149600","title":"Reduction in [18F]Nifene Binding, a PET imaging Probe for α4β2* Nicotinic acetylcholinergic receptors in Hippocampus-Subiculum of postmortem human Alzheimer’s disease brain","abstract":"Aβ, Tau, and α4β2* nAChRs in AD Subjects: Schematic showing three biomarkers for AD. (A). Imaging of Aβ plaques (senile plaques, SP) using PET are currently used in AD subjects. [ 18 F]Flotaza, an Aβ plaque imaging agent was used in this work. (B). PET imaging of tau (neurofibrillary tangles, NFT) is currently used in AD subjects. In this work, [ 125 I]IPPI was used to evaluate tau. (C). Cholinergic abnormalities are being investigated as potential biomarkers. In this work α4β2* nAChRs using [ 18 F]nifene has been evaluated. • Relationship of α4β2* nAChRs and Alzheimer’s disease Aβ plaque and Tau pathology. • [ 18 F]Nifene sufficiently detects α4β2* nAChRs in postmortem hippocampus-subiculum. • Decrease in [ 18 F]nifene with AD pathology progression in hippocampus-subiculum. • Negative correlation of α4β2* nAChRs levels with Aβ plaque and Tau AD pathology. • [ 18 F]Nifene PET may be useful for diagnostic and therapeutic monitoring in AD. Nicotinic acetylcholinergic receptors (nAChRs), including the α4β2* subtype are involved in cognition, learning and memory and may be adversely affected in Alzheimer’s disease (AD). In our efforts to consider translational use of [ 18 F]nifene PET in AD, we report quantitative autoradiographic evaluation of α4β2* nAChRs using hippocampus-subiculum (HP-SUB) from cognitively normal (CN) and AD subjects. Brain slices were incubated in [ 18 F]nifene for α4β2* nAChRs and adjacent sections were tested with [ 18 F]flotaza for Aβ plaques and [ 125 I]IPPI for tau. Anti-Aβ and anti-tau immunostaining were carried out on adjacent slices. Regions of interest were drawn and binding of [ 18 F]nifene, [ 18 F]flotaza and [ 125 I]IPPI were quantified. All CN subjects exhibited significant [ 18 F]nifene binding in the HP-SUB regions. Average [ 18 F]nifene ratios of SUB to HP was 1.9, suggesting higher α4β2* nAChRs in the SUB versus HP regions. [ 18 F]nifene binding did not change with aging in the female subjects, while the male subjects exhibited a weak positive correlation. There was a significant decrease in the binding of [ 18 F]nifene in AD subjects compared to CN. Braak stage comparisons showed a decrease of [ 18 F]nifene in stages V and VI, while [ 18 F]flotaza and [ 125 I]IPPI increased significantly. A negative correlation was observed between [ 18 F]nifene vs [ 18 F]flotaza and [ 18 F]nifene vs [ 125 I]IPPI across Braak stages I-VI. These findings suggest that α4β2* nAChR availability was effectively measured by [ 18 F]nifene in the HP-SUB and was adversely affected by the presence of Aβ plaques and tau.","journal":"Brain Research","year":2025,"id":520824,"datarank":0.2757851267403578,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.007021206356149573,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.007021206356149573,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8772,"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":1248870,"name":"Ambrose Loc T Ngo","orcid":"0009-0002-6993-9131","position":1,"is_corresponding":false},{"id":1109679,"name":"Tram B. Danh","orcid":null,"position":2,"is_corresponding":false},{"id":1065145,"name":"Brooke A. Delaney","orcid":null,"position":3,"is_corresponding":false},{"id":725634,"name":"Christopher Liang","orcid":"0000-0001-9081-294X","position":4,"is_corresponding":false},{"id":256002,"name":"Geidy E. Serrano","orcid":"0000-0002-9527-2011","position":5,"is_corresponding":false},{"id":107088,"name":"Thomas G. Beach","orcid":"0000-0003-3296-6128","position":6,"is_corresponding":false},{"id":579729,"name":"Jogeshwar Mukherjee","orcid":"0000-0003-1009-877X","position":7,"is_corresponding":false},{"id":1248871,"name":"Fariha Karim","orcid":"0009-0001-3104-9523","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:49:32.958846Z","pmid":"40154862","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":[]}