Study on the metabolism of Alzheimer's disease by PET

点击翻译按钮获取中文摘要

We could not perform the planned experiments on rat brain with positron emission tomography (PET) for animal use using carbon-11 labeled acetic acid, because of the default of cyclotron capacity. Instead, we did the experiments on the rat brain, in which cholinergic neurons in the basal forebrain were inhibited to produce acetylcholine by the injection of bromopyruvic acid. It is similar state to Alzheimer's brain in the depletion of acetylcholine in the cerebral cortex. We measured cerebral blood flow (CBF) and cerebral metabolic rate of glucose (CMRGlu) in conjunction with in vitro measurement of glucose metabolizing enzymes.We got the result concerning the glucose metabolism that the CMRGlu of the frontal cortex was substantially reduced after damage of cholinergic projection. In this situation, compartment analysis of 18-fluorodeoxyglucose disclosed the specific suppression of k3^*, which corresponds to hexokinase activity. We measured the glycolytic enzymes after PET scan in vitro, and found that there was no remarkable reduction of enzyme activities except for hexokinase, and that there was a close relationship between the hexokinase activities and k3^*. Concomitant with CMRGlu measurement, we examined CBF using 15-oxygen labeled water, and it disclosed that there was no apparent CBF decrease in the frontal cortex, where CMRGlu was low. This flow-metabolism uncoupling suggests that discrepancy between CMRGlu and oxygen metabolism seen in Alzheimer's disease, which we have reported in J Nucl Med, might be in part due to such flow-metabolism uncoupling.We are preparing the papers concerning the above mentioned results.