A 70-year-old woman with progressive dementia, rigidity, and supranuclear gaze palsy is found to have tau-positive neurofibrillary tangles in the substantia nigra, subthalamic nucleus, and globus pallidus on autopsy with 4-repeat tau isoforms. The diagnosis is:

• A Progressive supranuclear palsy (PSP) ✓
• B Corticobasal degeneration (CBD)
• C Frontotemporal dementia with MAPT mutation
• D Alzheimer's disease with Parkinson's features

Explanation

Progressive supranuclear palsy is a 4R-tauopathy characterised by accumulation of hyperphosphorylated 4-repeat tau isoforms in neurons, astrocytes, and oligodendrocytes in the subthalamic nucleus, globus pallidus, substantia nigra, and brainstem (pontine nuclei). The pathognomonic cell types are 'tufted astrocytes' and neurofibrillary tangles in the substantia nigra with globose morphology. Clinical features include vertical supranuclear gaze palsy (especially downgaze), postural instability with backward falls, dysarthria, and subcortical dementia. Corticobasal degeneration is also a 4R-tauopathy but shows cortical and basal ganglia involvement with 'astrocytic plaques'.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.