Publication date: Apr 15, 2025

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder with 4-repeat (R) tau protein deposition. The substantia nigra (SN) and midbrain tegmentum nuclei (MBT) are consistently affected. Lymphocyte infiltrates are scarce in the brain of neurodegenerative diseases, although a few reports have described this feature in brains with the α-synucleinopathy, Parkinson’s disease (PD). To evaluate cytotoxic T-cell response, serial sections spanning 120 microns of the SN were consecutively immunostained for phosphorylated tau (AT8) or α-synuclein, cytotoxic T-cell marker, and microglia marker HLA-DR. Sections were analyzed 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 were increased in the SN of PSP compared to PD and controls. T-cell/neuron contact was observed in PSP. In multivariate models, CD8 counts were not predicted by disease duration, younger age at death, and by the amount of p-tau pathology. SN and midbrain tegmentum showed more CD8 cells than the cortex. The presence of more prominent nigral cytotoxic T-cell response in PSP than in PD supports the notion that the common p-tau neuropathology in PSP might have potential relationships with autoimmune mechanisms.

Semantics

Original Article