Noninvasive assessment of aromatic L-amino acid decarboxylase activity in aging rhesus monkey brain in vivo

The effect of aging on aromatic L-amino acid decarboxylase (AAAD) activity in rhesus monkey striatum was assessed in vivo using PET imaging. Two analo gs of L-DOPA, 6-fluoro-m-tyrosine (FMT) and 6-fluoro-L-DOPA (FDOPA), were u sed to image rhesus monkeys of various ages. Results show that when the ani mals were grouped between young (3-11 years) and aged (25-37 years), FDOPA uptake in the older animals showed a 21% decline (P < 0.0005), while FMT up take in young and older animals were not different. On the other hand, when individual uptake values were plotted vs, age, linear regression analysis showed FDOPA uptake similarly declined with age (r = -0.84, P < 0.001) whil e FMT uptake increased with age (r = 0.66, P < 0.05). Since FMT pharmacokin etics has been shown to be unaffected by metabolic steps occurring after th e AAAD step, while FDOPA traces all the steps involved in L-DOPA metabolism , FMT is a suitable tracer to assess AAAD activity while FDOPA traces dopam ine turnover. Based on these tracer characteristics, this study found that AAAD activity is maintained or increased in the aging rhesus monkey striatu m while the FDOPA uptake decreases with age consistent with age-related dec lines in neuronal mechanisms whose overall effect is increased striatal dop amine turnover and clearance. Furthermore, comparison of results of this st udy with previous studies support the notion that the effect of aging in th e dopamine system is different from that of MPTP-induced parkinsonism. (C) 2001 Wiley-Liss, Inc.