An 80-year-old woman with slowly progressive dementia, difficulty walking, and urinary incontinence dies. Autopsy shows cortical atrophy predominantly in the frontal and temporal lobes. Microscopically, neuritic plaques (composed of amyloid beta core surrounded by dystrophic neurites) and neurofibrillary tangles (composed of hyperphosphorylated tau) are identified. The neurofibrillary tangles are composed of which specific structural protein?

• A Alpha-synuclein
• B Hyperphosphorylated tau (paired helical filaments) ✓
• C TDP-43
• D Prion protein (PrPSc)

Explanation

Alzheimer disease is a tauopathy; neurofibrillary tangles are composed of hyperphosphorylated tau protein assembled into paired helical filaments that accumulate within neuronal perikarya and processes. Tau normally stabilizes microtubules; hyperphosphorylation causes it to dissociate and aggregate. Alpha-synuclein forms Lewy bodies (Parkinson disease, DLB). TDP-43 aggregates are seen in ALS and frontotemporal dementia. Prion protein PrPSc accumulates in Creutzfeldt-Jakob disease.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.