title: Altered brain serotonin transporter and associated glucose metabolism in Alzheimer disease.
abstract: Whether preclinical depression is one of the pathophysiologic features of Alzheimer disease (AD) has been under debate. In vivo molecular imaging helps clarify this kind of issue. Here, we examined in vivo changes in the brain serotoninergic system and glucose metabolism by scanning early- to moderate-stage AD patients with and without depression using PET with a radiotracer for the serotonin transporter, (11)C-3-amino-4-(2-dimethylaminomethylphenylsulfanyl) benzonitrile (DASB), and a metabolic marker, (18)F-FDG.
  
  
  METHODS
  Fifteen AD patients (8 nondepressed and 7 depressed) and 10 healthy subjects participated. All participants underwent 3-dimensional MRI and quantitative (11)C-DASB PET measurements, followed by (18)F-FDG PET scans in the AD group. Region-of-interest analysis was used to examine changes in (11)C-DASB binding potential estimated quantitatively by the Logan plot method in the serotonergic projection region. In addition, statistical parametric mapping was used to examine whether glucose metabolism in any brain region correlated with levels of (11)C-DASB binding in the dense serotonergic projection region (striatum) in AD.
  
  
  RESULTS
  Psychologic evaluation showed that general cognitive function (Mini-Mental State Examination) was similar between the 2 AD subgroups. Striatal (11)C-DASB binding was significantly lower in AD patients, irrespective of depression, than in healthy controls (P < 0.05, corrected), and (11)C-DASB binding in other dense projection areas decreased significantly in the depressive group, compared with the control group. The (11)C-DASB binding potential levels in the subcortical serotonergic projection region correlated negatively with depression score (Spearman correlation, P < 0.01) but not with dementia score. Statistical parametric mapping correlation analysis showed that glucose metabolism in the right dorsolateral prefrontal cortex was positively associated with the level of striatal (11)C-DASB binding in AD.
  
  
  CONCLUSIONS
  The significant reduction in (11)C-DASB binding in nondepressed AD patients suggests that presynaptic serotonergic function is altered before the development of psychiatric problems such as depression in AD. The depressive AD group showed greater and broader reductions in binding, suggesting that a greater loss of serotonergic function relates to more severe psychiatric symptoms in the disease. This serotonergic dysfunction may affect the activity of the right dorsolateral prefrontal cortex, a higher center of cognition and emotion in AD.
authors.affiliation: Laboratory of Human Imaging Research, Molecular Imaging Frontier Research Center, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan. ouchi@hama-med.ac.jp
authors.forename: Yasuomi
authors.initials: Y
authors.lastname: Ouchi
authors.forename: Etsuji
authors.initials: E
authors.lastname: Yoshikawa
authors.forename: Masami
authors.initials: M
authors.lastname: Futatsubashi
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yagi
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Ueki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D000814:Aniline Compounds / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003863:Depression / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013440:Sulfides / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides; D019788:Fluorodeoxyglucose F18; D005947:Glucose