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Several observations suggest that the cortical lesions of progressive supranuclear palsy (PSP) play a role in the clinical symptoms and signs of the disease, although direct evidence for this is lacking. We addressed the significance of these lesions in a series of 10 cases of definite PSP. Tau positive cortical lesions were constant, and the mean density of neurofibrillary tangles (NFTs) was highest in the precentral and angular gyri. Their cortical distribution was singular: they were mainly located in the deepest cortical layers, affecting small as well as large neurons. They were weakly and rarely labelled with anti-ubiquitin antibodies. The tau metabolism impairment appeared more diffuse than previously thought, since neuropil threads, tau positive astrocytic tangles and oligodendroglial inclusions were also seen in the cortex and the subcortical structures. A factorial analysis of NFT density in cortex and subcortex isolated two factors, cortical and subcortical, both linked to the pedunculopontine nucleus. This suggests a prominent role of this nucleus in the spread of the lesions. A pathological subgroup exhibited mild lesions in the pedunculopontine nucleus, which were always associated with mild cortical density of NFTs. In this subgroup, the clinical data were unusual: absence of oculomotor palsy and axial rigidity in one case, of dementia in another, and presence of tremor at rest in the third case. The presence of cortical NFTs could be related to the selective involvement of cortical pathways perhaps connected with the pedunculopontine nucleus.

The significance of cortical pathology in progressive supranuclear palsy: Clinico-pathological data in 10 cases