A 60-year-old man has progressive asymmetric limb weakness with fasciculations, hyperreflexia, and extensor plantar responses, with intact sensation and cognition until late stages. Autopsy shows loss of anterior horn cells and lateral corticospinal tract pallor. Cytoplasmic inclusions in surviving neurons stain positive for which protein in the majority of sporadic cases?
- A Alpha-synuclein
- B Tau
- C TDP-43 ✓
- D Prion protein
Correct answer: C. TDP-43
Explanation
Amyotrophic lateral sclerosis is characterized by degeneration of lower motor neurons in the anterior horns and upper motor neurons in the corticospinal tracts. In most sporadic and familial cases, ubiquitinated cytoplasmic inclusions within motor neurons contain TDP-43; rare SOD1-mutant familial cases lack these inclusions. Alpha-synuclein marks Lewy body disease and multiple system atrophy, tau marks Alzheimer disease and frontotemporal dementias, and abnormal prion protein marks spongiform encephalopathies.
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.