THE AGING SUBSTANTIA-NIGRA - QUANTITATIVE HISTOLOGIC-STUDY

In this study, we estimated the amount of neuronal neuromelanin in hem atoxylin and eosin sections of the pars compacta of the substantia nig ra in 69 autopsied subjects, 14 to 100 years old. The mean area of cel lular neuromelanin showed a curvilinear increase from 103 mu m(2) at a ge 14, to 600 at age 67 before dropping off to 328 at age 100 (R(2)=+0 .51, p<0.00001). By contrast, the areal fraction or area of neuromelan in relative to the area of neuronal cell bodies showed a linear increa se with age (r=+0.84, p<0.00001). The latter and an increase in the pe rcent of neuromelanin pigmented neuronal cell bodies from 83% at age 1 4 to almost 100% at age 65 and older (R(2)=+0.61, P<0.00001) accounted for the increasing mean area of cellular neuromelanin. By contrast, a decrease in the mean area of neuronal cell bodies (r=-0.63, p<0.00001 ) and a decrease in the number of profiles of neuronal cell bodies (r= -0.51, p<0.0001) explained the deecrease of mean area of cellular neur omelanin beyond 67. Our findings support the hypothesis that an overlo ad of neuromelanin is neurotoxic and emphasize the importance of using age-matched controls in histopathologic studies of the substantia nig ra.