A 65-year-old man presents with rapidly progressive aphasia, behavioral disinhibition, and executive dysfunction over 18 months. MRI shows asymmetric frontal and temporal lobe atrophy (knife-edge atrophy). Histology shows Pick bodies (round tau-positive intracytoplasmic inclusions) in hippocampal dentate granule cells and cortical neurons. Which protein is the major component of these inclusions?

• A TDP-43
• B FUS protein
• C Alpha-synuclein
• D Tau (3R isoform predominant) ✓

Explanation

Pick disease (behavioral variant frontotemporal dementia with Pick bodies) is characterized by Pick bodies composed predominantly of 3-repeat (3R) tau protein. This distinguishes it from Alzheimer disease, which has both 3R and 4R tau in neurofibrillary tangles. TDP-43 is the major protein in most cases of frontotemporal lobar degeneration (FTLD-TDP) and ALS. FUS is seen in a subset of FTLD cases. Alpha-synuclein is the component of Lewy bodies in Parkinson disease and Lewy body dementia.

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.