{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:33:51Z","timestamp":1785418431672,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,8]]},"group-title":"Neuroscience","reference-count":63,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["AG029479"],"award-info":[{"award-number":["AG029479"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["AG077700"],"award-info":[{"award-number":["AG077700"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Non-motor symptoms in Parkinson\u2019s disease (PD) may be influenced by the \u03b14\u03b22* subtype of nicotinic acetylcholine receptors (nAChR) present in the hippocampus and subiculum. To continue efforts in PET diagnostics for PD, autoradiographic [\n                  <jats:sup>18<\/jats:sup>\n                  F]nifene binding to \u03b14\u03b22* nAChR was quantitively assessed in the hippocampus-subiculum (HP-SUB) of PD (n = 27; 14 males, 13 females) and cognitively normal (CN) (n = 32; 16 males, 16 females) cases. Anti-ubiquitin for Lewy body and anti-\u03b1-synuclein immunostaining on adjacent slices were analyzed in QuPath and [\n                  <jats:sup>18<\/jats:sup>\n                  F]nifene binding was quantified in OptiQuant. Subiculum had greater [\n                  <jats:sup>18<\/jats:sup>\n                  F]nifene binding (51% to 85%) compared to HP in all subjects. Significantly higher [\n                  <jats:sup>18<\/jats:sup>\n                  F]nifene binding (&gt;250%) was seen in PD SUB and PD HP compared to CN in both males and females. The grey matter (GM) to white matter (WM) ratio in PD=3.53 while CN=1.33, a &gt;150% increase in PD. Binding of [\n                  <jats:sup>18<\/jats:sup>\n                  F]nifene to GM and WM individually was &gt;250% greater in PD compared to CN. Male CN exhibited an increase while and male PD exhibited a significant decrease in [\n                  <jats:sup>18<\/jats:sup>\n                  F]nifene binding with aging, while females did not exhibit significant differences. In summary, \u03b14\u03b22* nAChR measured by [\n                  <jats:sup>18<\/jats:sup>\n                  F]nifene is significantly upregulated in the PD HP and SUB. This increased [\n                  <jats:sup>18<\/jats:sup>\n                  F]nifene binding may be of diagnostic value using PET imaging.\n                <\/jats:p>","DOI":"10.64898\/2026.04.07.716971","type":"posted-content","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T02:35:12Z","timestamp":1775702112000},"source":"Crossref","is-referenced-by-count":0,"title":["Increased Binding of [\n                  <sup>18<\/sup>\n                  F]Nifene, a PET Imaging Probe for \u03b14\u03b22* Nicotinic Acetylcholinergic Receptors in Hippocampus-Subiculum of Postmortem Human Parkinson\u2019s Disease Brain"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1009-877X","authenticated-orcid":false,"given":"Jogeshwar","family":"Mukherjee","sequence":"first","affiliation":[{"name":"Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3104-9523","authenticated-orcid":false,"given":"Fariha","family":"Karim","sequence":"additional","affiliation":[{"name":"Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6993-9131","authenticated-orcid":false,"given":"Allyson","family":"Ngo","sequence":"additional","affiliation":[{"name":"Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9081-294X","authenticated-orcid":false,"given":"Christopher","family":"Liang","sequence":"additional","affiliation":[{"name":"Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9527-2011","authenticated-orcid":false,"given":"Geidy E.","family":"Serrano","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute, Sun City, AZ 85351, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3296-6128","authenticated-orcid":false,"given":"Thomas G.","family":"Beach","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute, Sun City, AZ 85351, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041103351035000_2026.04.07.716971v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pbr.2022.01.011"},{"key":"2026041103351035000_2026.04.07.716971v1.2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.180737"},{"key":"2026041103351035000_2026.04.07.716971v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2009.11.004"},{"key":"2026041103351035000_2026.04.07.716971v1.4","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0538-8"},{"key":"2026041103351035000_2026.04.07.716971v1.5","doi-asserted-by":"publisher","DOI":"10.1111\/neup.12189"},{"key":"2026041103351035000_2026.04.07.716971v1.6","doi-asserted-by":"publisher","DOI":"10.1002\/syn.22016"},{"key":"2026041103351035000_2026.04.07.716971v1.7","doi-asserted-by":"publisher","DOI":"10.1002\/jlcr.4071"},{"key":"2026041103351035000_2026.04.07.716971v1.8","doi-asserted-by":"publisher","DOI":"10.1002\/syn.21530"},{"key":"2026041103351035000_2026.04.07.716971v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00377-X"},{"key":"2026041103351035000_2026.04.07.716971v1.10","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26237360"},{"key":"2026041103351035000_2026.04.07.716971v1.11","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-024-00687-6"},{"key":"2026041103351035000_2026.04.07.716971v1.12","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-191683"},{"key":"2026041103351035000_2026.04.07.716971v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2006.05.036"},{"key":"2026041103351035000_2026.04.07.716971v1.14","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3242-07.2007"},{"key":"2026041103351035000_2026.04.07.716971v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(92)90244-6"},{"key":"2026041103351035000_2026.04.07.716971v1.16","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-003-2259-9"},{"key":"2026041103351035000_2026.04.07.716971v1.17","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20688"},{"key":"2026041103351035000_2026.04.07.716971v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2024.12.008"},{"key":"2026041103351035000_2026.04.07.716971v1.19","doi-asserted-by":"publisher","DOI":"10.3390\/biom15040592"},{"key":"2026041103351035000_2026.04.07.716971v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-0618(02)00100-X"},{"key":"2026041103351035000_2026.04.07.716971v1.21","doi-asserted-by":"publisher","DOI":"10.1111\/cns.70069"},{"key":"2026041103351035000_2026.04.07.716971v1.22","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-023-00676-7"},{"key":"2026041103351035000_2026.04.07.716971v1.23","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.112.103846"},{"key":"2026041103351035000_2026.04.07.716971v1.24","doi-asserted-by":"publisher","DOI":"10.1177\/10738584211011979"},{"key":"2026041103351035000_2026.04.07.716971v1.25","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.665820"},{"key":"2026041103351035000_2026.04.07.716971v1.26","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2014.00213"},{"key":"2026041103351035000_2026.04.07.716971v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2025.149600"},{"key":"2026041103351035000_2026.04.07.716971v1.28","doi-asserted-by":"publisher","DOI":"10.3390\/biom15121686"},{"key":"2026041103351035000_2026.04.07.716971v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2009.74"},{"key":"2026041103351035000_2026.04.07.716971v1.30","doi-asserted-by":"publisher","DOI":"10.1134\/S1990750817040035"},{"key":"2026041103351035000_2026.04.07.716971v1.31","doi-asserted-by":"publisher","DOI":"10.2174\/0929867325666180410105135"},{"key":"2026041103351035000_2026.04.07.716971v1.32","doi-asserted-by":"publisher","DOI":"10.1002\/syn.21981"},{"key":"2026041103351035000_2026.04.07.716971v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2021.09.018"},{"key":"2026041103351035000_2026.04.07.716971v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101834"},{"key":"2026041103351035000_2026.04.07.716971v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2015.11.018"},{"key":"2026041103351035000_2026.04.07.716971v1.36","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2025.1535310"},{"key":"2026041103351035000_2026.04.07.716971v1.37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055886"},{"key":"2026041103351035000_2026.04.07.716971v1.38","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12259"},{"key":"2026041103351035000_2026.04.07.716971v1.39","doi-asserted-by":"publisher","DOI":"10.1126\/science.1227157"},{"key":"2026041103351035000_2026.04.07.716971v1.40","doi-asserted-by":"publisher","DOI":"10.1162\/imag_a_00397"},{"key":"2026041103351035000_2026.04.07.716971v1.41","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9591524.0321"},{"key":"2026041103351035000_2026.04.07.716971v1.42","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2009.106"},{"key":"2026041103351035000_2026.04.07.716971v1.43","doi-asserted-by":"publisher","DOI":"10.1177\/1877718X241313373"},{"key":"2026041103351035000_2026.04.07.716971v1.44","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.676257"},{"key":"2026041103351035000_2026.04.07.716971v1.45","doi-asserted-by":"publisher","DOI":"10.3390\/cells11244000"},{"key":"2026041103351035000_2026.04.07.716971v1.46","doi-asserted-by":"publisher","DOI":"10.1002\/cne.24320"},{"key":"2026041103351035000_2026.04.07.716971v1.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2014.10.021"},{"key":"2026041103351035000_2026.04.07.716971v1.48","doi-asserted-by":"publisher","DOI":"10.3390\/receptors4010007"},{"key":"2026041103351035000_2026.04.07.716971v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2007.02.014"},{"key":"2026041103351035000_2026.04.07.716971v1.50","doi-asserted-by":"publisher","DOI":"10.1124\/mol.110.067561"},{"key":"2026041103351035000_2026.04.07.716971v1.51","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)00410-7"},{"key":"2026041103351035000_2026.04.07.716971v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(99)00146-3"},{"key":"2026041103351035000_2026.04.07.716971v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2005.12.017"},{"key":"2026041103351035000_2026.04.07.716971v1.54","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300302"},{"key":"2026041103351035000_2026.04.07.716971v1.55","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00161"},{"key":"2026041103351035000_2026.04.07.716971v1.56","doi-asserted-by":"publisher","DOI":"10.1124\/pr.110.003269"},{"key":"2026041103351035000_2026.04.07.716971v1.57","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-10059-1"},{"key":"2026041103351035000_2026.04.07.716971v1.58","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25853"},{"key":"2026041103351035000_2026.04.07.716971v1.59","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl5163"},{"key":"2026041103351035000_2026.04.07.716971v1.60","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.121.263198"},{"key":"2026041103351035000_2026.04.07.716971v1.61","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308041200"},{"key":"2026041103351035000_2026.04.07.716971v1.62","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-202465"},{"key":"2026041103351035000_2026.04.07.716971v1.63","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2484-21.2022"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.04.07.716971","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T10:35:17Z","timestamp":1775903717000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.04.07.716971"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,8]]},"references-count":63,"URL":"https:\/\/doi.org\/10.64898\/2026.04.07.716971","relation":{},"subject":[],"published":{"date-parts":[[2026,4,8]]},"subtype":"preprint"}}