{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T16:44:07Z","timestamp":1789922647717,"version":"4.0.1"},"reference-count":67,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T00:00:00Z","timestamp":1677110400000},"content-version":"vor","delay-in-days":0,"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":["NIH AG029479"],"award-info":[{"award-number":["NIH AG029479"]}],"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":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Since cholinergic dysfunction has been implicated in Alzheimer's disease (AD), the effects of A\u03b2 plaques on nicotinic acetylcholine receptors (nAChRs) \u03b14\u03b22* subtype were studied using the transgenic 5xFAD mouse model of AD. Using the PET radiotracer [<jats:sup>18<\/jats:sup>F]nifene for \u03b14\u03b22* nAChRs, in vitro autoradiography and in vivo PET\/CT studies in 5xFAD mice were carried out and compared with wild\u2010type (C57BL\/6) mice. Ratios of [<jats:sup>18<\/jats:sup>F]nifene binding in\u00a0brain\u00a0regions\u00a0versus cerebellum (CB) in 5xFAD mice brains were\u00a0for thalamus (TH) = 17, hippocampus\u2010subiculum = 7, frontal cortex (FC) = 5.5, and striatum = 4.7. [<jats:sup>125<\/jats:sup>I]IBETA and immunohistochemistry (IHC) in 5xFAD brain slices confirmed A\u03b2 plaques. Nicotine and acetylcholine displaced [<jats:sup>18<\/jats:sup>F]nifene in 5xFAD mice (IC<jats:sub>50<\/jats:sub> nicotine = 31\u201373\u00a0nM; ACh = 38\u201383\u00a0nM) and C57BL\/6 (IC<jats:sub>50<\/jats:sub> nicotine = 16\u201318\u00a0nM; ACh = 34\u201355\u00a0nM). Average [<jats:sup>18<\/jats:sup>F]nifene SUVR (CB as reference) in 5xFAD\u00a0mice\u00a0was\u00a0significantly\u00a0higher\u00a0in FC = 3.04\u00a0compared\u00a0to C57BL\/6\u00a0mice FC = 1.92 (<jats:italic>p<\/jats:italic> = .001), whereas TH difference between 5xFAD\u00a0mice (SUVR = 2.58) and C57BL\/6\u00a0mice (SUVR = 2.38) was not significant. Nicotine\u2010induced dissociation half life (t<jats:sub>1\/2<\/jats:sub>) of [<jats:sup>18<\/jats:sup>F]nifene for TH were 37 min for 5xFAD\u00a0mice and 26 min for C57BL\/6\u00a0mice. Dissociation\u00a0half\u00a0life\u00a0 for FC\u00a0in\u00a0C57BL\/6\u00a0mice was\u00a077 min , while no dissociation of [<jats:sup>18<\/jats:sup>F]nifene occurred in the\u00a0medial\u00a0prefrontal\u00a0cortex (mFC) of 5xFAD mice. Coregistration of [<jats:sup>18<\/jats:sup>F]nifene PET with MR suggested that\u00a0the mPFC, and anterior cingulate (AC) regions exhibited\u00a0high uptake in 5xFAD mice\u00a0compared\u00a0to\u00a0C57BL\/6\u00a0mice. Ex vivo [<jats:sup>18<\/jats:sup>F]nifene and in vitro [<jats:sup>125<\/jats:sup>I]IBETA A\u03b2 plaque autoradiography after in vivo PET\/CT scan of 5xFAD mouse brain were moderately correlated (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup> = 0.68). In conclusion, 5xFAD mice showed increased non\u2010displaceable [<jats:sup>18<\/jats:sup>F]nifene binding in mPFC.<\/jats:p>","DOI":"10.1002\/syn.22265","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T22:38:23Z","timestamp":1675809503000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Abnormal [<sup>18<\/sup>F]NIFENE binding in transgenic 5xFAD mouse model of Alzheimer's disease: In vivo PET\/CT imaging studies of \u03b14\u03b22* nicotinic acetylcholinergic receptors and in vitro correlations with A\u03b2 plaques"],"prefix":"10.1002","volume":"77","author":[{"given":"Christopher","family":"Liang","sequence":"first","affiliation":[{"name":"Preclinical Imaging Department of Radiological Sciences University of California\u2010Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace A.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Preclinical Imaging Department of Radiological Sciences University of California\u2010Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tram B.","family":"Danh","sequence":"additional","affiliation":[{"name":"Preclinical Imaging Department of Radiological Sciences University of California\u2010Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anoopraj K.","family":"Sandhu","sequence":"additional","affiliation":[{"name":"Preclinical Imaging Department of Radiological Sciences University of California\u2010Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lusine L.","family":"Melkonyan","sequence":"additional","affiliation":[{"name":"Preclinical Imaging Department of Radiological Sciences University of California\u2010Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amina U.","family":"Syed","sequence":"additional","affiliation":[{"name":"Preclinical Imaging Department of Radiological Sciences University of California\u2010Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jogeshwar","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Preclinical Imaging Department of Radiological Sciences University of California\u2010Irvine  Irvine California 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