|Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
We have developed a method to measure acetylcholinesterase (AChE) activity, a marker of cholinergic neuronal function, in the brain by positron emission tomography (PET). An analog of acetyIcholine, N-methyl-4-piperidyl acetate (MP4A), was labeled with carbon-11, and brain AChE activity was measured quantitatively using [^<11>C]MP4A.A three-compartment model was applied to calculate regional brain AChE activity using metabolite corrected arterial plasma input function. In Alzheimer's disease (n=19), there was a significant reduction (-24%) of AChE activity in the cerebral cortex, amygdala, and hippocampus compared with age-matched normal controls (n=14). There was a significant inverse correlation between cortical AChE activity and severity of dementia in Alzheimer's disease, supporting cholinergic hypothesis of dementia in Alzheimer's disease. No age effect was seen in normal controls (n=23) ranging in age 24 to 89 years. The results suggest that Alzheimer's disease is not an exaggerated form of normal aging. In Parkinson's disease (n=16), AChE activity in the cerebral cortex and thalamus was often reduced, especially in advanced and demented patients. In progressive supranuclear palsy (PSP : n=12), there was a marked reduction of AChE activity in the thalamus, suggesting that there was a preferential loss of cholinergic system in the brainstem. When the thalamic to cerebral cortical AChE actitity ratio was taken for each subject, Parkinson's disease and PSP were separated, suggesting that PET measurement of AChE activity may be useful for differentiating the two similar disorders.