title: Comparing α7 nicotinic acetylcholine receptor binding, amyloid-β deposition, and mitochondria complex-I function in living brain: A PET study in aged monkeys.
abstract: This study was aimed to assess the correlations among α7 nicotinic acetylcholine receptor (α7-nAChR) binding, amyloid-β (Aβ) deposition, and mitochondrial complex I (MC-I) activity in the brain of aged monkeys (Macaca mulatta). Positron emission tomography (PET) measurements with [(11) C](R)-MeQAA, [(11) C]PIB, and [(18) F]BCPP-EF were conducted in monkeys in a conscious condition. [(11) C](R)-MeQAA binding was analyzed by a simplified reference tissue model to calculate nondisplaceable binding potential (BPND), [(11) C]PIB uptake was calculated by standard uptake value ratio (SUVR), and [(18) F]BCPP-EF binding was determined by Logan graphical analysis to calculate total distribution volume (VT) with arterial blood sampling. Higher brain uptake was determined in the thalamus, hippocampus, striatum, and cortical regions for [(11) C](R)-MeQAA, while being lower in the cerebellum. Significant age-related reduction of [(11) C](R)-MeQAA binding to α7-nAChR was determined only in the occipital cortex. The plot of Vt of [(18) F]BCPP-EF against BPND of [(11) C](R)-MeQAA indicated a significant negative correlation in the hippocampus and cortical regions in aged animals. Plotting of SUVR of [(11) C]PIB against BPND of [(11) C](R)-MeQAA showed a positive correlation. The in vivo binding of [(11) C](R)-MeQAA could reflect the upregulation of α7-nAChR induced by neurodegenerative damage determined by Aβ deposition as well as impaired MC-I activity in living brain.
authors.affiliation: Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, 434-8601, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Nishiyama
authors.affiliation: Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, 434-8601, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohba
authors.affiliation: Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, 434-8601, Japan.
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Kanazawa
authors.affiliation: Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, 434-8601, Japan.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Kakiuchi
authors.affiliation: Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, 434-8601, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Tsukada
mesh_terms: D000375:Aging; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D000814:Aniline Compounds / Q000493:pharmacokinetics; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D042967:Electron Transport Complex I / Q000378:metabolism*; D021621:Imaging, Three-Dimensional; D008253:Macaca mulatta; D008297:Male; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D013747:Tetrabenazine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D013844:Thiazoles / Q000493:pharmacokinetics; D014851:Wakefulness; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
chemical_list: C575320:(11C)-(+)-alpha-dihydrotetrabenazine; C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D002247:Carbon Isotopes; D013844:Thiazoles; D064569:alpha7 Nicotinic Acetylcholine Receptor; D042967:Electron Transport Complex I; D013747:Tetrabenazine
keywords: Amyloid-β; Mitochondria complex I; [11C](R)-MeQAA; [11C]PIB; [18F]BCPP-EF; α7 nicotinic receptor