Visualization of monoamine oxidase in human brain.

11973 Monoamine oxidase (MAO; EC: 1.4.3.4) is a flavin containing enzyme which exists in two subtypes, MA0 A and MA0 B. MA0 A and B are different gene products and they also differ in their substrate and inhibitor selectivities and their cellular localizations. In human brain MA0 B predominates (B:A = 4:l) and is largely compartmentalized in cell bodies of serotonergic neurons and in glia. Many studies of human brain MA0 B post mortem report that MA0 B increases with age and in neurodegenerative disease [I]. This is consistent with investigations showing that the number of glial cells increases with age in the normal human brain [2] and in neurodegenerative disease. As an initial step in the investigation of the feasibility of detecting and tracking neurodegenerative processes in the living human brain, we measured brain MA0 B in normal healthy subjects (n=21; age range 23-86; 9 females and 12 males; non-smokers). The studies followed the guidelines of the Human Subjects Research Committee at Brookhaven National Laboratory and subjects gave informed consent after the procedures had been explained t o them. We used PET and deuterium substituted [11C]L-deprenyl([11C]L-deprenyl-D2) [SI. MA0 B was assessed using a model term ilk3 which is a function of MA0 B activity. A blood t o brain influx constant (IC1) which is related to brain blood flow was also calculated. Regions of interest were occipital cortex, frontal cortex, cingulate gyrus, parietal cortex, temporal cortex, pons, thalamus, basal ganglia, cerebellum and global regions. The regional distribution of MA0 B was highest in the basal ganglia and the thalamus with intermediate levels in the frontal cortex and cingulate gyrus and lowest levels in the parietal and temporal cortices and cerebellum. The model termilks showed a significant increase with age (p<0.004) in all brain regions examined except for the cingulate gyrus (with a trend for the parietal cortex). The results of correlation analysis for the global region is shown in Figure IA. .The same patterns remained when the correlation analysis was performed separately for males and females. [%!]L-Deprenyl-D2 has tracer characteristics which allow a plasma to brain transfer constant, a model term which is related to blood flow, t o be extracted from dynamic PET data. In contrast to ilk3 which increased with age, Ki SignXcantly (p<O.Ol) decreased in all brain regions except for the pons and the cerebellum. The highest correlation coefficients were in the cingulate gyrus, the frontal …