A 68-year-old man presents with early falls, vertical gaze palsy (especially downward gaze), axial rigidity, and pseudobulbar palsy. He dies of pneumonia 6 years later. Autopsy reveals atrophy of the midbrain with loss of pigment from the locus coeruleus. Microscopy shows globose neurofibrillary tangles and tufted astrocytes in the brainstem. The primary protein abnormality is:

• A Alpha-synuclein aggregation
• B Amyloid-beta deposition
• C TDP-43 proteinopathy
• D Tau protein (4-repeat tau) aggregation ✓

Explanation

This describes progressive supranuclear palsy (PSP, Steele-Richardson-Olszewski disease), a 4-repeat tauopathy. The characteristic findings are vertical supranuclear gaze palsy, early postural instability, and midbrain atrophy with globose NFTs and tufted astrocytes. Alpha-synuclein is seen in Parkinson's and Lewy body dementia. TDP-43 is seen in ALS and frontotemporal dementia. Amyloid-beta is seen in Alzheimer disease.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.