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

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

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.

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Funding

This study was funded by the University of Leipzig; there was no involvement in the study design; in the collection, analysis and interpretation of the data; in the writing of the report; and in the decision to submit the paper for publication.

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Nuclear Medicine, University of Leipzig, Liebigstr. 18, 04103, Leipzig, Germany

    Kai Kendziorra, Philipp Mael Meyer, Henryk Barthel, Swen Hesse, Georg Alexander Becker, Julia Luthardt, Andreas Schildan, Marianne Patt, Dietlind Sorger, Anita Seese & Osama Sabri

  2. Department of Psychiatry, University of Leipzig, Semmelweisstr. 10, 04103, Leipzig, Germany

    Henrike Wolf & Herman-Josef Gertz

  3. Department of Old Age Psychiatry and Psychiatry Research, Psychiatric University Hospital (PUK) Zurich, University of Zurich, Minervastr. 145, 8032, Zurich, Switzerland

    Henrike Wolf

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  1. Kai Kendziorra
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Correspondence to Kai Kendziorra.

Additional information

The asterisk used in the receptor nomenclature means that the receptor complex may contain additional subunits.

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Kendziorra, K., Wolf, H., Meyer, P.M. et al. Decreased cerebral α4β2* nicotinic acetylcholine receptor availability in patients with mild cognitive impairment and Alzheimer’s disease assessed with positron emission tomography. Eur J Nucl Med Mol Imaging 38, 515–525 (2011). https://doi.org/10.1007/s00259-010-1644-5

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  • DOI: https://doi.org/10.1007/s00259-010-1644-5

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