Decreased cerebral α4β2* nicotinic acetylcholine receptor availability in patients with mild cognitive impairment and Alzheimer's disease assessed with positron emission tomography.
OBJECTIVE
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-[(18)F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[(18)F]FA-85380) PET. After coregistration with individual magnetic resonance imaging the binding potential (BP(ND)) of 2-[(18)F]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-[(18)F]FA-85380 BP(ND) in typical AD-affected brain regions. Thereby, the corpus callosum was identified as the most suitable reference region. The 2-[(18)F]FA-85380 BP(ND) 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-[(18)F]FA-85380 BP(ND).


CONCLUSIONS
2-[(18)F]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-[(18)F]FA-85380 PET might give prognostic information about a conversion from MCI to AD.
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany. K.Kendziorra@t-online.de
Kai
K
Kendziorra
Henrike
H
Wolf
Philipp Mael
PM
Meyer
Henryk
H
Barthel
Swen
S
Hesse
Georg Alexander
GA
Becker
Julia
J
Luthardt
Andreas
A
Schildan
Marianne
M
Patt
Dietlind
D
Sorger
Anita
A
Seese
Herman-Josef
HJ
Gertz
Osama
O
Sabri
D000544:Alzheimer Disease / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D000647:Amnesia / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D001384:Azetidines / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012984:Software
C119803:2-fluoro-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D001798:Blood Proteins; D011725:Pyridines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2