A 62-year-old man presents with progressive asymmetric limb weakness, fasciculations, and hyperreflexia over 18 months, with no sensory deficits and no sphincter involvement. Autopsy shows loss of motor neurons in the anterior horns and hypoglossal nucleus with gliosis, and residual neurons contain ubiquitinated cytoplasmic inclusions. The protein accumulating in these inclusions is:

• A Alpha-synuclein
• B Tau
• C Superoxide dismutase 1
• D TDP-43 ✓

Explanation

Amyotrophic lateral sclerosis combines upper and lower motor neuron signs without sensory loss. Most sporadic cases show TDP-43 positive ubiquitinated cytoplasmic inclusions in degenerating motor neurons, reflecting abnormal nuclear clearance of this RNA-binding protein. Mutant superoxide dismutase 1 accounts for about 20 percent of familial ALS and forms its own inclusions, but it is not the protein in the common sporadic inclusion. Alpha-synuclein marks Parkinson disease and tau marks frontotemporal degeneration.

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.