| First Author | Liang C | Year | 2023 |
| Journal | Synapse | Volume | 77 |
| Issue | 3 | Pages | e22265 |
| PubMed ID | 36749986 | Mgi Jnum | J:350144 |
| Mgi Id | MGI:7662495 | Doi | 10.1002/syn.22265 |
| Citation | Liang C, et al. (2023) Abnormal [(18) F]NIFENE binding in transgenic 5xFAD mouse model of Alzheimer's disease: In vivo PET/CT imaging studies of alpha4beta2* nicotinic acetylcholinergic receptors and in vitro correlations with Abeta plaques. Synapse 77(3):e22265 |
| abstractText | Since cholinergic dysfunction has been implicated in Alzheimer's disease (AD), the effects of Abeta plaques on nicotinic acetylcholine receptors (nAChRs) alpha4beta2* subtype were studied using the transgenic 5xFAD mouse model of AD. Using the PET radiotracer [(18) F]nifene for alpha4beta2* 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 Abeta 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 Abeta 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. |
