Autopsy of an 80-year-old with Parkinson's disease reveals depigmentation of the substantia nigra. Microscopy shows eosinophilic intracytoplasmic inclusions in surviving neurons. These inclusions are composed primarily of which abnormally aggregated protein?

• A Tau protein (neurofibrillary tangles)
• B TDP-43 (TAR DNA-binding protein)
• C Alpha-synuclein (Lewy bodies) ✓
• D Huntingtin protein aggregates

Explanation

Lewy bodies are the pathological hallmark of Parkinson's disease and Lewy body dementia, consisting of intracytoplasmic rounded eosinophilic inclusions with a dense core and pale halo. They are composed primarily of aggregated, hyperphosphorylated, and ubiquitinated alpha-synuclein (SNCA), a presynaptic protein. SNCA gene duplications/triplications and point mutations (A53T, A30P) cause familial PD. Tau aggregates characterize Alzheimer's (NFTs) and CTE. TDP-43 aggregates are found in ALS and frontotemporal lobar degeneration.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.