Nicotinic Receptors in the CNS as Visualized by Positron Emission Tomography

Alzheimer’s disease, senile dementia of Alzheimer type (AD/SDAT) is a progressive neurodegenerative disease which entity can be described in terms of clinical symptoms, neuropsychological tests and laboratory investigations during life and postmortem histopathological examinations. For the definitive diagnosis of AD/SDAT both clinical and histopathological investigations are required. Improved diagnostic resolution is needed since there is still some lack of agreement between histopathological and clinical diagnosis. Neurochemical studies performed in autopsy or biopsy brain tissue have revealed that AD/SDAT afflicts several neurotransmitter system in the brain. Among them the cholinergic system is the one that shows the most consistent changes and also best correlates with cognitive function. Presynaptic cholinergic defects are present in autopsy AD/SDAT brain tissue such as losses in choline acetyltransferase activity, synthesis and release of acetylcholine and nicotinic receptors. Positron emission tomography (PET) is a technique suitable for in vivo studies of neuronal activity in the brain. PET has already shown a great potential for psychopharmacological research. Is it possible to study central cholinergic activity in vivo by PET? This strategy was initiated using 11C-choline (Gauthier et. al., 1985; Eckernas et al. 1985). A low penetration of intact 11C-choline to the brain combined with a rapid conversion of formed 11C-acetylcholine to labelled metabolites hampered this effort. An alternative to measuring precursor transport and transmitter turnover would be to study the cholinergic receptors in brain.