Acetylcholine receptors in dementia and mild cognitive impairment.
OBJECTIVE
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).


METHODS
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.


CONCLUSIONS
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.
Sabri
Osama
O
Department of Nuclear Medicine, University of Leipzig, Stephanstrasse 11, Leipzig, Germany. osama.sabri@medizin.uni-leipzig.de
Kendziorra
Kai
K
Wolf
Henrike
H
Gertz
Hermann-Josef
HJ
Brust
Peter
P
D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003072:Cognition Disorders / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003704:Dementia / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D015336:Molecular Probe Techniques; D049268:Positron-Emission Tomography / Q000379:methods; D011950:Receptors, Cholinergic / Q000378:metabolism*; D014018:Tissue Distribution
D011950:Receptors, Cholinergic