Original Article

European Journal of Nuclear Medicine and Molecular Imaging

, Volume 38, Issue 3, pp 515-525

First online:

Decreased cerebral α4β2* nicotinic acetylcholine receptor availability in patients with mild cognitive impairment and Alzheimer’s disease assessed with positron emission tomography

  • Kai KendziorraAffiliated withDepartment of Nuclear Medicine, University of Leipzig Email author 
  • , Henrike WolfAffiliated withDepartment of Psychiatry, University of LeipzigDepartment of Old Age Psychiatry and Psychiatry Research, Psychiatric University Hospital (PUK) Zurich, University of Zurich
  • , Philipp Mael MeyerAffiliated withDepartment of Nuclear Medicine, University of Leipzig
  • , Henryk BarthelAffiliated withDepartment of Nuclear Medicine, University of Leipzig
  • , Swen HesseAffiliated withDepartment of Nuclear Medicine, University of Leipzig
  • , Georg Alexander BeckerAffiliated withDepartment of Nuclear Medicine, University of Leipzig
  • , Julia LuthardtAffiliated withDepartment of Nuclear Medicine, University of Leipzig
  • , Andreas SchildanAffiliated withDepartment of Nuclear Medicine, University of Leipzig
  • , Marianne PattAffiliated withDepartment of Nuclear Medicine, University of Leipzig
    • , Dietlind SorgerAffiliated withDepartment of Nuclear Medicine, University of Leipzig
    • , Anita SeeseAffiliated withDepartment of Nuclear Medicine, University of Leipzig
    • , Herman-Josef GertzAffiliated withDepartment of Psychiatry, University of Leipzig
    • , Osama SabriAffiliated withDepartment of Nuclear Medicine, University of Leipzig

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Abstract

Purpose

Postmortem studies indicate a loss of nicotinic acetylcholine receptor (nAChRs) in Alzheimer’s disease (AD). In order to establish whether these changes in the cholinergic system occur at an early stage of AD, we carried out positron emission tomography (PET) with a specific radioligand for the α4β2* nicotinic acetylcholine receptor (α4β2* nAChR) in patients with mild to moderate AD and in patients with amnestic mild cognitive impairment (MCI), who have a high risk to progress to AD.

Methods

Nine patients with moderate AD, eight patients with MCI and seven age-matched healthy controls underwent 2-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]FA-85380) PET. After coregistration with individual magnetic resonance imaging the binding potential (BPND) of 2-[18F]FA-85380 was calculated using either the corpus callosum or the cerebellum as reference regions. PET data were analysed by region of interest analysis and by voxel-based analysis.

Results

Both patients with AD and MCI showed a significant reduction in 2-[18F]FA-85380 BPND in typical AD-affected brain regions. Thereby, the corpus callosum was identified as the most suitable reference region. The 2-[18F]FA-85380 BPND correlated with the severity of cognitive impairment. Only MCI patients that converted to AD in the later course (n = 5) had a reduction in 2-[18F]FA-85380 BPND.

Conclusion

2-[18F]FA-85380 PET appears to be a sensitive and feasible tool for the detection of a reduction in α4β2* nAChRs which seems to be an early event in AD. In addition, 2-[18F]FA-85380 PET might give prognostic information about a conversion from MCI to AD.

Keywords

Nicotinic acetylcholine receptors 2-[18F]FA-85380 Alzheimer’s disease MCI PET