In vivo detection of neurotransmitter changes in Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is characterized by multiple deficits of neurotransmitters in brain. These observations are mainly based upon studies in postmortem brain material where the disease has reached a terminal state. In order to obtain further insight into the early disturbances of the neurotransmitter activities in AD, new imaging techniques such as positron emission tomography (PET) and single positron emission tomography (SPECT) can be applied in vivo for detection of neurotransmitter activity in normal as well as AD brains. Nicotinic receptors have been traced in AD patients by PET and 11C-nicotine at different stages of AD. A lower uptake of (R)(+)- compared to (S)(-)-11C-nicotine was observed in AD patients while the difference in uptake of the two enantiomers was less pronounced in normal individuals. A positive correlation has been observed between cognitive function (Mini-Mental-State-Examination) and uptake of (S)(-)-11C-nicotine in the temporal cortex of AD patients. 11C-benztropine has been used to measure muscarinic receptors in brain by PET. Oral tacrine treatment (80 mg daily) restore nicotinic receptors in AD patients as visualized by PET and 11C-nicotine. Kinetic analysis indicate increased binding of (S)(-)-11C-nicotine after 3 months of treatment with tacrine. The PET data are paralleled by improvement in neuropsychological testings. Intraventricular infusion of nerve growth factor (NGF) to an AD patients for 3 months resulted in an transient increase in uptake and binding of (S)(-)-11C-nicotine in the temporal and frontal cortex and a persistent increase in cortical blood flow.