Four-Repeat Tauopathy With PSP-Like Features in Severe Intellectual Disability: Two Autopsy Cases.

Autopsy of two adults with lifelong severe intellectual disability revealed four-repeat tauopathy. One case showed typical progressive supranuclear palsy, whereas the other demonstrated a PSP-like phenotype with restricted basal ganglia-brainstem involvement. Molecular autopsy identified variants in SPG7 and CTSD, suggesting intracellular vulnerability. These findings expand the neuropathological spectrum of severe intellectual disability and indicate that primary four-repeat tauopathy may occur in this underrecognised population.