Human cerebral acetylcholinesterase activity measured with positron emission tomography: procedure, normal values and effect of age

Abstract.

The regional cerebral metabolic rate of [¹¹C]N-methyl-4-piperidyl acetate, which is nearly proportional to regional cerebral acetylcholinesterase (AChE) activity, was measured by dynamic positron emission tomography in 20 healthy subjects with a wide age range (24–89 years). Quantitative measurement was achieved using a kinetic model which consisted of arterial plasma and cerebral tissue compartments. The plasma input function was obtained using thin-layer chromatography and an imaging phosphor plate system at frequent sampling intervals to catch the rapid metabolism of the tracer in the blood. The distribution of the rate constant k ₃, an index of AChE activity, agreed well with reported post-mortem AChE distribution in the cerebral cortex (0.067–0.097 min^–1) and thalamus (0.268 min^–1), where AChE activity was low to moderate. The k ₃ values in the striatum and cerebellum, where AChE activity was very high, did not respond linearly to AChE activity because of increased flow dependency. No significant effect of age was found on AChE activity of the cerebral cortex, suggesting that the ascending central cholinergic system is preserved in normal aging. This study has shown that quantitative measurement of enzyme activity in the living brain is possible through appropriate modelling of tracer kinetics and accurate measurement of the input function. The method should be applicable to patients with Alzheimer’s disease and those with other kinds of dementia whose central cholinergic system has been reported to be disturbed.