Acetylcholine receptors in dementia and mild cognitive impairment.

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-[(18)F]F-A-85380, which is supposed to be specific for alpha4beta2 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 alpha4beta2 nAChRs in brain regions typically affected by AD pathology. These findings indicate that a reduction in alpha4beta2 nAChRs occurs during early symptomatic stages of AD. The alpha4beta2 nAChR availability in these regions correlated with the severity of cognitive impairment, indicating a stage sensitivity of the alpha4beta2 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-[(18)F]F-A-85380, we developed the new alpha4beta2 nAChR-specific radioligands (+)- and (-)-[(18)F]norchloro-fluoro-homoepibatidine (NCFHEB) and evaluated them preclinically. (-)-[(18)F]NCFHEB shows twofold higher brain uptake and significantly shorter acquisition times. Therefore, (-)-[(18)F]NCFHEB should be a suitable radioligand for larger clinical investigations.

• Authors: Osama Sabri, Kai Kendziorra, Henrike Wolf, Hermann-Josef Gertz, Peter Brust
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 35 Suppl 1 Pg. S30-45 (Mar 2008) ISSN: 1619-7070 [Print] Germany
• PMID: 18228017 (Publication Type: Journal Article, Review)

Chemical References

• Receptors, Cholinergic

Topics

• Brain (diagnostic imaging, metabolism)
• Cognition Disorders (complications, diagnostic imaging, metabolism)
• Dementia (complications, diagnostic imaging, metabolism)
• Humans
• Molecular Probe Techniques
• Positron-Emission Tomography (methods)
• Receptors, Cholinergic (metabolism)
• Tissue Distribution