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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

01.03.2008

Acetylcholine receptors in dementia and mild cognitive impairment

verfasst von: Osama Sabri, Kai Kendziorra, Henrike Wolf, Hermann-Josef Gertz, Peter Brust

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Sonderheft 1/2008

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Abstract

Purpose

To clarify whether changes in the cholinergic transmission occur early in the course of Alzheimer’s disease (AD), we carried out positron emission tomography (PET) with the radioligand 2-[¹⁸F]F-A-85380, which is supposed to be specific for α4β2 nicotinic acetylcholine receptors (nAChRs).

Method

We included patients with moderate to severe AD and patients with amnestic mild cognitive impairment (MCI), presumed to present preclinical AD.

Results

Both patients with AD and MCI showed significant reductions in α4β2 nAChRs in brain regions typically affected by AD pathology. These findings indicate that a reduction in α4β2 nAChRs occurs during early symptomatic stages of AD. The α4β2 nAChR availability in these regions correlated with the severity of cognitive impairment, indicating a stage sensitivity of the α4β2 nAChR status.

Conclusion

Together, our results provide evidence for the potential of 2-[¹⁸]F-A-85380 nAChR PET in the diagnosis of patients at risk for AD. Because of the extraordinary long acquisition time with 2-[¹⁸F]F-A-85380, we developed the new α4β2 nAChR-specific radioligands (+)- and (−)-[¹⁸F]norchloro-fluoro-homoepibatidine (NCFHEB) and evaluated them preclinically. (−)-[¹⁸F]NCFHEB shows twofold higher brain uptake and significantly shorter acquisition times. Therefore, (−)-[¹⁸F]NCFHEB should be a suitable radioligand for larger clinical investigations.

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Titel: Acetylcholine receptors in dementia and mild cognitive impairment
verfasst von: Osama Sabri
Kai Kendziorra
Henrike Wolf
Hermann-Josef Gertz
Peter Brust
Publikationsdatum: 01.03.2008
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe Sonderheft 1/2008
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-007-0701-1

Springer Medizin

Abstract

Purpose

Method

Results

Conclusion

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