PROGRESSIVE SUPRANUCLEAR PALSY AFFECTS BOTH THE SUBSTANTIA-NIGRA PARSCOMPACTA AND RETICULATA

We have analyzed the neuropathology of the substantia nigra in four ca ses of progressive supranuclear palsy compared with age-matched contro ls and patients with Parkinson's disease. Although there are many repo rts of severe dopaminergic cell loss in progressive supranuclear palsy , the fate of the GABAergic pars reticulata neurones remains unclear. Serial section analysis and fractional counts of pars compacta neurone s (identified by their neuromelanin pigment) and pars reticulata neuro nes (identified using parvalbumin immunohistochemistry) were performed , and the type and distribution of neuropathology were described. Seve re neurodegeneration within the dopaminergic pars compacta was seen in all cases of progressive supranuclear palsy and all cases of Parkinso n's disease compared with controls. Lewy body pathology was found only in cases of Parkinson's disease, while neurofibrillary tangles were s een only in cases of progressive supranuclear palsy. Tau-positive astr ocytes and neuropil threads were occasionally seen in controls and cas es of Parkinson's disease (particularly those of advanced age) but wer e extremely numerous in all cases of progressive supranuclear palsy. T here was a similar decrease in parvalbumin immunoreactivity within the pars reticulata in both progressive supranuclear palsy and Parkinson' s disease. However, there was a striking 70% reduction in the number o f pars reticulata neurones in progressive supranuclear palsy, with no cell loss observed in Parkinson's disease compared with controls. Our results show that both the dopaminergic pars compacta and the GABAergi c pars reticulata are significantly damaged in cases of progressive su pranuclear palsy. The distribution of neurodegeneration in patients wi th Parkinson's disease and progressive supranuclear palsy is discussed with respect to the current theories on pathophysiology in basal gang lia circuitry. (C) 1997 Academic Press.