Pathology · CNS Pathology (Tumors, Degenerative, Infections)

A 70-year-old man with progressive dementia has autopsy findings of neurofibrillary tangles in the entorhinal cortex and hippocampus, amyloid plaques, and cortical atrophy. The protein within neurofibrillary tangles is:

  • A Alpha-synuclein forming Lewy bodies
  • B Hyperphosphorylated tau (microtubule-associated protein) forming paired helical filaments
  • C TDP-43 forming cytoplasmic inclusions
  • D Mutant huntingtin forming intranuclear inclusions
Correct answer: B. Hyperphosphorylated tau (microtubule-associated protein) forming paired helical filaments

Explanation

Neurofibrillary tangles (NFTs) in Alzheimer disease consist of paired helical filaments (PHF) of abnormally hyperphosphorylated tau protein. Tau normally stabilizes microtubules; hyperphosphorylation dissociates tau from microtubules, impairing axonal transport, and the free tau aggregates into PHF. Braak staging tracks NFT progression from entorhinal cortex → hippocampus → association cortices → primary cortices. Alpha-synuclein forms Lewy bodies in Parkinson disease and DLB. TDP-43 inclusions occur in ALS and FTLD-TDP. Huntingtin intranuclear inclusions are pathognomonic of Huntington disease.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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