Histopathology of the substantia nigra in Alzheimer's disease.

Histopathologic examination of the pars compacta of the substantia nigra of 17 patients with Alzheimer's disease showed Lewy bodies in six, neurofibrillary tangles in another six and only histologic changes that did not differ from age-matched controls in five patients. Four of the six patients with nigral Lewy bodies showed severe loss of neural cell bodies, reactive astrocytosis, gliosis and neuromelanin in macrophages and in the neuropile. By contrast, the loss of neuronal cell bodies in our patients without nigral Lewy bodies regardless of whether or not they also had nigral neurofibrillary tangles was no greater than what we observed in our age-matched controls. Quantitative cell counts confirmed our histopathologic estimates of neuronal loss. Our study and the findings of others show that the substantia nigra is often abnormal in Alzheimer's disease and that the abnormalities are rarely severe without nigral Lewy bodies.

Immunohistochemical analysis of c-Fos and c-Jun in retinoblastoma.

The c-fos promoter is negatively regulated by the retinoblastoma (Rb)-susceptibility-gene-encoded protein as well as by other genes involved in the control of transcription, cell cycle regulation and neoplastic transformation. We have examined by immunohistochemistry the c-Fos and c-Jun proteins in five cases of retinoblastoma in order to evaluate eventual alterations in their expression in vivo, possibly related to a gene mutation or to loss of Rb negative control.

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.

Lack of detection of p53 expression in retinoblastoma tumor cells.

p53 was examined by immunohistochemistry in five cases of retinoblastoma, a neoplasm that is caused by a loss of function of the Retinoblastoma susceptibility gene (Rb), mapped to chromosome 13q14. Object of the study was the identification of eventual further gene mutation in retinoblastoma tumor cells determining the onset of an independent tumoral monoclonal cell subset. We did not observe any positive reaction for p53 protein expression in the five cases we analyzed.

Nigral degeneration in acquired immune deficiency syndrome (AIDS).

Using stereological techniques we have estimated the volume density of melanin and counted the number of pigmented and non-pigmented neuronal cell bodies in the pars compacta of the substantia nigra of 12 autopsied patients with acquired immune deficiency syndrome (AIDS) who did not have inflammation or necrosis of the midbrain or clinical parkinsonism. The total number of neuronal cell bodies was 25% lower in AIDS (P less than 0.01) than in 12 age-matched controls, although the volume density of neuronal melanin did not differ from that of controls because the percentage of pigmented cell bodies was higher (P less than 0.01) and the cell bodies were more fully packed with melanin in AIDS. Also, the expected increase with age of the volume density of neuronal melanin (P less than 0.02) and the percentage of pigmented neurons (P less than 0.01) occurred in the controls but not in AIDS patients. Importantly, our histopathological examination showed unequivocal nigral degeneration with neuronal loss, small neuronal cell bodies packed with melanin, reactive astrocytosis and extra-cellular melanin in the AIDS patients but not in controls. Our study shows that a subclinical nigral degeneration is common in AIDS and could possibly explain the heightened susceptibility of some patients to drug-induced parkinsonism.