A 50-year-old man develops progressive weakness of hand muscles, fasciculations, hyperreflexia, and dysphagia. MRI shows no compressive lesion. Pathologic examination would show degeneration of both upper and lower motor neurons. Aggregates of which protein are found in the remaining motor neurons?
- A Alpha-synuclein
- B TDP-43 (TAR DNA-binding protein 43) ✓
- C Tau
- D Huntingtin
Correct answer: B. TDP-43 (TAR DNA-binding protein 43)
Explanation
The clinical picture describes amyotrophic lateral sclerosis (ALS), involving simultaneous degeneration of upper motor neurons (corticospinal tract) and lower motor neurons (anterior horn cells and cranial nerve nuclei). The pathologic hallmark in the majority of ALS cases is cytoplasmic inclusions of TDP-43 (encoded by TARDBP gene). TDP-43 mislocalization from the nucleus to cytoplasm, where it forms ubiquitinated aggregates, is central to ALS pathogenesis. SOD1 mutations cause a minority of familial ALS cases with distinct inclusions.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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