Loss of non-phosphorylated neurofilament immunoreactivity, with preservation of tyrosine hydroxylase, in surviving substantia nigra neurons in Parkinson's disease.
The distribution of neurofilament immunoreactivity in the substantia nigra was examined by immunohistochemistry in five patients dying with Parkinson's disease and six control patients dying without neurological disease. In controls, pigmented neurons in the substantia nigra were intensively labelled by SMI32, a monoclonal antibody to non-phosphorylated neurofilament protein. In the substantia nigra from patients who had Parkinson's disease, there was a pronounced reduction of SMI32 labelling intensity in surviving pigmented neurons. By contrast, tyrosine hydroxylase immunoreactivity in surviving pigmented neurons was normal. SMI32 labelling was normal in regions of the brainstem not affected by the neuropathological process of Parkinson's disease. Findings with either antibodies to phosphorylated neurofilament, or enzymatic dephosphorylation followed by SMI32 labelling, indicated that loss of SMI32 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 destroyed by the neuropathological process of Parkinson's disease. Nevertheless, the normal appearance of tyrosine hydroxylase indicates that protein synthesising systems may be intact in surviving neurons. Loss of neurofilament immunoreactivity may prove a sensitive neuropathological marker for characterisation of degenerating neurons in Parkinson's disease.
Gai
W P
WP
Department of Physiology, Flinders University, Bedford Park, SA, Australia.
Vickers
J C
JC
Blumbergs
P C
PC
Blessing
W W
WW
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D010300:Parkinson Disease / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D013378:Substantia Nigra / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D016900:Neurofilament Proteins; D014446:Tyrosine 3-Monooxygenase