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α4β2 nicotinic receptor status in Alzheimer’s disease using 123I-5IA-85380 SPECT
  1. J T O’Brien (j.t.o'brien{at}ncl.ac.uk)
  1. University of Newcastle upon Tyne, United Kingdom
    1. S J Colloby (s.j.colloby{at}ncl.ac.uk)
    1. University of Newcastle upon Tyne, United Kingdom
      1. S Pakrasi (sanjeet.pakrasi{at}ncl.ac.uk)
      1. University of Newcastle upon Tyne, United Kingdom
        1. E K Perry (e.k.perry{at}ncl.ac.uk)
        1. Newcastle General Hospital, United Kingdom
          1. S L Pimlott (gcl515{at}clinmed.gla.ac.uk)
          1. University of Glasgow, United Kingdom
            1. D J Wyper (gpca12{at}udcf.gla.ac.uk)
            1. University of Glasgow, United Kingdom
              1. I G McKeith (i.g.mckeith{at}ncl.ac.uk)
              1. University of Newcastle, United Kingdom
                1. E D Williams (david.williams{at}chs.northy.nhs.uk)
                1. Regional Medical Physics Department, United Kingdom

                  Abstract

                  Objective: Loss of the α4β2 nicotinic receptor subtype is found at autopsy in Alzheimer’s disease. We investigated in vivo changes in this receptor using SPECT with 123I-5-Iodo-3-[2(S)- 2-azetidinylmethoxy] pyridine (5IA-85380), a novel nicotinic acetylcholine receptor ligand which binds predominantly to the α4β2 receptor.

                  Methods: 32 subjects (16 Alzheimer’s disease (AD) and 16 elderly controls) underwent 123I-5IA-85380 and perfusion (99mTc-HMPAO) SPECT scanning. Region of interest analysis was performed with cerebellar normalization.

                  Results: Significant bilateral reductions in nicotinic receptor binding were identified in frontal (left, p=0.004; right, p=0.002), striatal (left, p=0.004; right, p=0.003), right medial temporal (p=0.04) and pons (p<0.001) in AD compared to controls. There were no significant correlations with clinical or cognitive measures. The pattern of nicotinic binding significantly differed from that of perfusion in both AD subjects and controls. Both 123I-5IA-85380 and 99mTc-HMPAO SPECT imaging demonstrated similar diagnostic performance in correctly classifying controls and AD patients.

                  Conclusion: Using 123I-5IA-85380 SPECT we found changes consistent with significant reductions in the nicotinic α4β2 receptor in cortical and striatal brain regions. This method could facilitate diagnosis and may be useful for monitoring disease progression and response to treatment in AD and related diseases.

                  • Alzheimer's disease
                  • SPECT
                  • nicotinic
                  • region of interest

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