LOSS OF NONPHOSPHORYLATED NEUROFILAMENT IMMUNOREACTIVITY, WITH PRESERVATION OF TYROSINE-HYDROXYLASE, IN SURVIVING SUBSTANTIA-NIGRA NEURONS IN PARKINSONS-DISEASE

The distribution of neurofilament immunoreactivity in the substantia n igra was examined by immunohistochemistry in five patients dying with Parkinson's disease and six control patients dying without neurologica l disease. In controls, pigmented neurons in the substantia nigra were intensively labelled by SMI32, a monoclonal antibody to non-phosphory lated neurofilament protein. In the substantia nigra from patients who had Parkinson's disease, there was a pronounced reduction of SMI32 la belling intensity in surviving pigmented neurons. By contrast, tyrosin e hydroxylase immunoreactivity in surviving pigmented neurons was norm al. SMI32 labelling was normal in regions of the brainstem not affecte d by the neuropathological process of Parkinson's disease. Findings wi th either antibodies to phosphorylated neurofilament, or enzymatic dep hosphorylation followed by SMI32 labelling, indicated that loss of SMI 32 immunostaining in Parkinson's disease was not due to masking of the neurofilament epitopes by phosphorylation. Our results indicate that neurofilament proteins are particularly likely to be disrupted or dest royed by the neuropathological process of Parkinson's disease. Neverth eless, the normal appearance of tyrosine hydroxylase indicates that pr otein synthesising systems may be intact in surviving neurons. Loss of neurofilament immunoreactivity may prove a sensitive neuropathologica l marker for characterisation of degenerating neurons in Parkinson's d isease.