Aging produces a specific pattern of striatal dopamine loss: implications for the etiology of idiopathic Parkinson's disease.
To examine the possible causal contribution of normal or accelerated aging to the neurodegenerative process of Parkinson's disease, we measured the influence of aging on subregional striatal dopamine and homovanillic acid levels in postmortem brain of 23 neurologically and psychiatrically normal human subjects 14-92 years old. We observed a significant decline in striatal dopamine levels and increase in the homovanillic acid/dopamine molar ratios with increasing age. The dopamine loss, on average, was of the same magnitude in the caudate nucleus and the putamen (-60% in the 84-year-old group as compared with the 22-year-old group), with the caudal component of both nuclei being more affected than the rostral subdivisions. The level of subregional dopamine metabolism, as measured by the homovanillic acid/dopamine ratio, in our young individuals (mean age, 22 years) was found to be inversely correlated to the degree of subregional dopamine loss suffered by the individuals in the older age groups. We conclude the following: (a) Striatal subdivisions with physiologically higher dopamine metabolism are not at a greater risk of suffering dopamine neuronal damage with advancing age, as would seem to be implied by the oxidative stress hypothesis; thus, formation of dopamine-derived oxy radicals in the human striatum appears unlikely to be a primary factor responsible for the age-related striatal dopamine loss. (b) The regional and subregional pattern of striatal dopamine loss in normal aging differs substantially from the pattern typically observed in idiopathic Parkinson's disease; therefore, the cause of idiopathic Parkinson's disease cannot be primarily an age-dependent neurodegenerative process.
Kish
S J
SJ
Human Brain Laboratory, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
Shannak
K
K
Rajput
A
A
Deck
J H
JH
Hornykiewicz
O
O
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000209:etiology* / Q000378:metabolism; D012016:Reference Values; D014018:Tissue Distribution
D004298:Dopamine; D006719:Homovanillic Acid