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α4β2 nicotinic receptor status in Alzheimer’s disease using 123I-5IA-85380 single-photon-emission computed tomography
  1. J T O’Brien1,
  2. S J Colloby1,
  3. S Pakrasi1,
  4. E K Perry1,
  5. S L Pimlott2,
  6. D J Wyper3,
  7. I G McKeith1,
  8. E D Williams4
  1. 1Institute for Ageing and Health, Newcastle University, Wolfson Research Centre, Newcastle General Hospital, Newcastle upon Tyne, UK
  2. 2West of Scotland Radionuclide Dispensary, North Glasgow University Hospitals NHS Trust, Western Infirmary, Glasgow, UK
  3. 3Department of Clinical Physics, South Glasgow University Hospitals NHS Trust, Southern General Hospital, Glasgow, UK
  4. 4Regional Medical Physics Department, Sunderland Royal Hospital, Sunderland, UK
  1. Correspondence to:
 Dr S J Colloby
 Institute for Ageing and Health, Newcastle University, Wolfson Research Centre, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK; s.j.colloby{at}ncl.ac.uk

Abstract

Background: Loss of the α4β2 nicotinic receptor subtype is found at autopsy in Alzheimer’s disease.

Objective: To investigate in vivo changes in this receptor using single-photon-emission CT (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 non-smoking subjects (16 with Alzheimer’s disease and 16 normal elderly controls) underwent 123I-5IA-85380 and perfusion (99mTc-hexamethylenepropyleneamine oxime (HMPAO)) SPECT scanning. Region of interest analysis was performed with cerebellar normalisation.

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 patients with 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 patients with AD and controls. Both 123I-5IA-85380 and 99mTc-HMPAO SPECT imaging demonstrated similar diagnostic performance in correctly classifying controls and patients with AD.

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 progression of the disease and response to treatment in patients with AD and related diseases.

  • CAMCOG, Cambridge Cognitive Examination
  • DLB, dementia with Lewy bodies
  • HMPAO, hexamethylenepropyleneamine oxime
  • MMSE, Mini-Mental State Examination
  • nAChR, nicotinic acetylcholine receptor
  • NPI, Neuropsychiatric Inventory
  • PET, positron emission tomography
  • rCBF, regional cerebral blood flow
  • ROI, region of interest
  • SPECT, single-photon-emission
  • 5IA-85380, 5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine

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Footnotes

  • Published Online First 29 November 2006

  • Competing interests: None.

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