Striatal 3,4-dihydroxyphenylalanine decarboxylase in aging: disparity between postmortem and positron emission tomography studies?
Recent positron emission tomography (PET) studies using 3,4-[18F]fluorodihydroxyphenylalanine ([18F]fluorodopa) have reported little or no decrement in dopaminergic function in human striatum (caudate and putamen) during aging. In contrast, previous postmortem studies have reported marked age-dependent decreases in the activity of dopa decarboxylase (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 subjects ranging in age from 17 to 103 years. We found a significant, albeit modest, age-dependent decrease in the concentration of DDC protein in caudate (r = -0.50, p < 0.05) but not in putamen (r = -0.16, p > 0.05), 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 of a robust effect of aging upon striatal DDC protein is consistent with the [18F]fluorodopa-PET studies that report either no change or only a relatively small decrease in striatal 18F accumulation during aging. To the extent that aging is associated with a substantial loss of striatal dopaminergic nerve terminals, the present results also suggest that DDC protein synthesis may be upregulated in those dopaminergic neurons that survive the aging process and, therefore, that striatal [18F]fluorodopa uptake indices may provide an overestimate of the number of dopaminergic nerve terminals during physiological aging.
Kish
S J
SJ
Human Neurochemical Pathology Laboratory, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
Zhong
X H
XH
Hornykiewicz
O
O
Haycock
J W
JW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000201:enzymology*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004296:Dopa Decarboxylase / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014055:Tomography, Emission-Computed
C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004296:Dopa Decarboxylase; D004298:Dopamine