STRIATAL 3,4-DIHYDROXYPHENYLALANINE DECARBOXYLASE IN AGING - DISPARITY BETWEEN POSTMORTEM AND POSITRON EMISSION TOMOGRAPHY STUDIES

Recent positron emission tomography (PET) studies using 3,4-[F-18] flu orodihydroxyphenylalanine ([F-18]fluorodopa) have reported little or n o decrement in dopaminergic function in human striatum (caudate and pu tamen) during aging. In contrast, previous postmortem studies have rep orted marked age-dependent decreases in the activity of dopa decarboxy lase (DDC), a variable upon which the PET determinations depend. Using quantitative blot immunolabeling techniques, we measured DDC protein concentrations in postmortem striata of 28 neurologically normal subje cts ranging in age from 17 to 103 years. We found a significant, albei t modest, age-dependent decrease in the concentration of DDC protein i n caudate (r = -0.50, p < 0.05) but not in putamen (r = -0.16, p > 0.0 5), with mean values of the 87-year-old group being 27% (caudate) and 12% (putamen) lower than those of the 30-year-old group, The absence o f a robust effect of aging upon striatal DDC protein is consistent wit h the [F-18]fluorodopa-PET studies that report either no change or onl y a relatively small decrease in striatal F-18 accumulation during agi ng. To the extent that aging is associated with a substantial loss of striatal dopaminergic nerve terminals, the present results also sugges t that DDC protein synthesis may be upregulated in those dopaminergic neurons that survive the aging process and, therefore, that striatal [ F-18]fluorodopa uptake indices may provide an overestimate of the numb er of dopaminergic nerve terminals during physiological aging.