Lewy bodies in Parkinson disease are intracytoplasmic eosinophilic inclusions composed of misfolded aggregates of which protein?

• A Tau (hyperphosphorylated, forming neurofibrillary tangles)
• B Ubiquitin (forming nuclear inclusions in FTLD)
• C TDP-43 (cytoplasmic inclusions in ALS and FTLD-TDP)
• D Alpha-synuclein (misfolded into fibrillar aggregates) ✓

Explanation

Lewy bodies are the pathological hallmark of Parkinson disease and Lewy body dementia; they are round, eosinophilic, intraneuronal cytoplasmic inclusions with a dense core and pale halo, composed predominantly of misfolded aggregated alpha-synuclein along with ubiquitin and neurofilament proteins. Hyperphosphorylated tau forms neurofibrillary tangles (Alzheimer disease, CTE, PSP). TDP-43 cytoplasmic inclusions are the hallmark of ALS and most cases of FTLD. Nuclear ubiquitin inclusions are seen in FTLD-FUS and some polyglutamine diseases.

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

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