The aging substantia nigra: quantitative histologic study

In this study, we estimated the amount of neuronal neuromelanin in hematoxylin and eosin sections of the pars compacta of the substantia nigra in 69 autopsied subjects, 14 to 100 years old. The mean area of cellular neuromelanin showed a curvilinear increase from 103 microns2 at age 14, to 600 at age 67 before dropping off to 328 at age 100 (R2 = +0.51, p < 0.00001). By contrast, the areal fraction or area of neuromelanin relative to the area of neuronal cell bodies showed a linear increase with age (r = +0.84, p < 0.00001). The latter and an increase in the percent of neuromelanin pigmented neuronal cell bodies from 83% at age 14 to almost 100% at age 65 and older (R2 = +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 decrease of mean area of cellular neuromelanin beyond 67. Our findings support the hypothesis that an overload of neuromelanin is neurotoxic and emphasize the importance of using age-matched controls in histopathologic studies of the substantia nigra.