title: Cross sectional PET study of cerebral adenosine A₁ receptors in premanifest and manifest Huntington's disease.
abstract: OBJECTIVE
  To study cerebral adenosine receptors (AR) in premanifest and manifest stages of Huntington's disease (HD).
  
  
  METHODS
  We quantified the cerebral binding potential (BP ND) of the A₁AR in carriers of the HD CAG trinucleotide repeat expansion using the radioligand [(18) F]CPFPX and PET. Four groups were investigated: (i) premanifest individuals far (preHD-A; n = 7) or (ii) near (preHD-B; n = 6) to the predicted symptom onset, (iii) manifest HD patients (n = 8), and (iv) controls (n = 36).
  
  
  RESULTS
  Cerebral A₁AR values of preHD-A subjects were generally higher than those of controls (by up to 31%, p < .01, in the thalamus on average). Across stages a successive reduction of A₁AR BPND was observed to the levels of controls in preHD-B and undercutting controls in manifest HD by down to 25%, p < .01, in the caudatus and amygdala. There was a strong correlation between A₁AR BP ND and years to onset. Before onset of HD, the assumed annual rates of change of A₁AR density were -1.2% in the caudatus, -1.7% in the thalamus and -3.4% in the amygdala, while the corresponding volume losses amounted to 0.6%, 0.1% and 0.2%, respectively.
  
  
  CONCLUSIONS
  Adenosine receptors switch from supra to subnormal levels during phenoconversion of HD. This differential regulation may play a role in the pathophysiology of altered energy metabolism.
authors.affiliation: Institute of Neuroscience and Medicine (INM-2), Forschungszentrum Jülich, 52425, Jülich, Germany, a.matusch@fz-juelich.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Matusch
authors.forename: Carsten
authors.initials: C
authors.lastname: Saft
authors.forename: David
authors.initials: D
authors.lastname: Elmenhorst
authors.forename: Peter H
authors.initials: PH
authors.lastname: Kraus
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Andreas
authors.initials: A
authors.lastname: Bauer
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000175:diagnosis / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D014018:Tissue Distribution; D014970:Xanthines / Q000493:pharmacokinetics*
chemical_list: C468796:8-cyclopenta-3-(3-fluoropropyl)-1-propylxanthine; D019275:Radiopharmaceuticals; D043682:Receptor, Adenosine A1; D014970:Xanthines