Whilst many reports mention neurofibrillary tangle the thalamus in progressive supranuclear palsy. These findings have several implications. The caudal pathology in the thalamus in progressive supranuclear intralaminar thalamus appears to be one of three basal palsy, there has been little detailed regional analysis of ganglia sites commonly affected in both progressive the distribution and density of thalamic pathology in this supranuclear palsy and Parkinson's disease. These sites disease or

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... other parkinsonian syndromes. The caudal are the dopaminergic substantia nigra, the cholinergic intralaminar thalamic nuclei are the major thalamic pedunculopontine tegmental nucleus and, from our regulators of the caudate nucleus and putamen, areas results, the glutamatergic caudal intralaminar thalamus. known to be dysfunctional in progressive supranuclear In both diseases these sites contain characteristic but palsy and Parkinson's disease. We investigated whether different pathologies, indicating disease-specific these thalamic nuclei degenerate in patients with these mechanisms of neurodegeneration. Interestingly, the disorders compared with age-matched, neurologically proportion of remaining neurons affected by these normal controls. Neurofibrillary tangle and Lewy body pathologies is low. This may indicate additional (possibly pathology was assessed and unbiased optical disector common) cellular mechanisms responsible for the methods were used to quantify total neuronal number. degeneration in these regions. Both the dopaminergic Despite different thalamic pathology, there was a dramatic nigra and the glutamatergic caudal intralaminar thalamus reduction in the total neuronal number in the caudal are the major regulators of basal ganglia function via the intralaminar nuclei in both progressive supranuclear caudate nucleus and putamen. The pedunculopontine palsy and Parkinson's disease (40-55% loss). In contrast, tegmental nucleus has major projections to both of these there was no loss of volume or total neuronal number in regulators. These findings indicate that dysregulation of the limbic thalamic nuclei in either disease group, two neurotransmitter systems within the basal ganglia indicating selective degeneration of the caudal may underlie common parkinsonian symptoms in these intralaminar nuclei. In Parkinson's disease, Lewy bodies disorders. For patients with Parkinson's disease, this loss were found in these regions, while in progressive of glutamate regulation may help explain some problems supranuclear palsy abundant intracellular neurofibrillary with dopamine replacement therapies, particularly over tangles and glial tangles concentrated in the caudal time. For patients with progressive supranuclear palsy, intralaminar nuclei. However, tangle formation accounted more widespread degeneration of basal ganglia structures would contribute to poor treatment outcomes. for only a small proportion of cell loss (ഛ10%) in Keywords: progressive supranuclear palsy; Parkinson's disease; limbic thalamic nuclei; caudal intralaminar thalamic nuclei Abbreviations: AP ϭ anterior principal nucleus; CM ϭ centromedian nucleus; MD ϭ mediodorsal nucleus; NFT ϭ neurofibrillary tangles; Pf ϭ parafascicular nucleus; PSP ϭ progressive supranuclear palsy