Midbrain cytotoxic T cells as a distinct neuropathological feature of progressive supranuclear palsy

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Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by four-repeat (4R) tau protein deposition. The substantia nigra (SN) and midbrain tegmentum nuclei (MBT) are consistently affected. Lymphocyte infiltrates are scarce in the brains of patients with neurodegenerative diseases, although a few reports have described their presence in the α-synucleinopathy Parkinson's disease (PD). To evaluate the cytotoxic T-cell response, serial sections spanning 120 μm of the SN were immunostained consecutively for phosphorylated tau (p-tau, AT8) or α-synuclein, cytotoxic T-cell marker and microglia marker HLA-DR. Sections were analysed with stereology software in 9 patients with PSP, 10 with PD and 6 healthy controls. We semiquantitatively scored CD8-positive cells in further brain regions. CD8 lymphocyte cell counts and microglial activation in the SN were higher in PSP than PD and controls. Furthermore, T-cell/neuron contact was observed in PSP. In multivariate models, CD8 counts were not predicted by disease duration, younger age at death or the amount of p-tau pathology. The SN and midbrain tegmentum showed more CD8 cells than the cortex. A more prominent nigral cytotoxic T-cell response in PSP than PD supports the suggestion that p-tau neuropathology in PSP might have potential relationships with autoimmune mechanisms.

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