Imaging of nicotinic and muscarinic receptors in Alzheimer's disease: Effect of tacrine treatment

Functional imaging techniques offer new possibilities for further understanding of changes in functional correlates of structural and biological changes in dementia disorders like Alzheimer's disease (AD). Regional disturbances in glucose metabolism and cerebral blood flow are known to occur in AD brains and probably roughly correlate to changes in neurotransmitter activities. A proper estimate would be to visualize the neuroreceptors themselves. In this study the cholinergic nicotinic and muscarinic receptors were studied in brain by positron emission tomography (PET). The rate constant k(2)* (s) (-)C-11-nicotine was significantly higher (+43%) in temporal cortex of AD patients compared to controls (p < 0.017) indicating a lower binding of C-11-nicotine in AD brains compared to controls. Treatment with the cholinesterase inhibitor tacrine (80 mg daily) during 3 months to AD patients resulted in a mean plasma concentration of 7.7 +/- 0.8 ng/ml and a corresponding inhibition of the cholinesterase activity in plasma by 34 +/- 5%. A significantly lower k(2)* (increased binding) for C-11-nicotine binding (-15%; p < 0.006) was obtained in the temporal cortex after 3 months of treatment compared to prior treatment. The muscarinic antagonist C-11-benztropine was used to visualize muscarinic receptors and the binding capacity of C-11-benztropine (K-R) was found to be decreased in the temporal cortex after 3 months of tacrine treatment.