title: Low density of sigma1 receptors in early Alzheimer's disease.
abstract: OBJECTIVE
  The sigma(1) receptor is considered to be involved in cognitive function. A postmortem study reported that the sigma(1) receptors were reduced in the hippocampus in Alzheimer's disease (AD). However, in vivo imaging of sigma(1) receptors in the brain of AD patients has not been reported. The aim of this study is to investigate the mapping of sigma(1) receptors in AD using [(11)C]SA4503 positron emission tomography (PET).
  
  
  METHODS
  We studied five AD patients and seven elderly volunteers. A dynamic series of decay-corrected PET data acquisition was performed for 90 min starting at the time of the injection of 500 MBq of [(11)C]SA4503. A two-tissue three-compartment model was used to estimate K (1), k (2), k (3), k (4), and the delay between metabolite-corrected plasma and tissue time activity using a Gauss-Newton algorithm. The ratio of k (3) to k (4) was computed as the binding potential (BP), which is linearly related to the density of sigma(1) receptors. Unpaired t tests were used to compare K (1) and BP in patients with AD and normal subjects.
  
  
  RESULTS
  As compared with normals, BP in the AD was significantly lower in the frontal, temporal, and occipital lobe, cerebellum and thalamus, whereas K (1) was significantly lower in the parietal lobe.
  
  
  CONCLUSIONS
  [(11)C]SA4503 PET can demonstrate that the density of cerebral and cerebellar sigma(1) receptors is reduced in early AD.
authors.affiliation: Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. mishina@nms.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Mishina
authors.forename: Masashi
authors.initials: M
authors.lastname: Ohyama
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishii
authors.forename: Shin
authors.initials: S
authors.lastname: Kitamura
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kimura
authors.forename: Kei-ichi
authors.initials: K
authors.lastname: Oda
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kawamura
authors.forename: Toru
authors.initials: T
authors.lastname: Sasaki
authors.forename: Shiro
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Katayama
authors.forename: Kiichi
authors.initials: K
authors.lastname: Ishiwata
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology*; D001923:Brain Chemistry; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000473:pathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D010879:Piperazines / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017480:Receptors, sigma / Q000032:analysis* / Q000737:chemistry; D013788:Thalamus / Q000000981:diagnostic imaging / Q000473:pathology; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D010879:Piperazines; D019275:Radiopharmaceuticals; D017480:Receptors, sigma; C101789:SA 4503