A biopsy from the temporal lobe of a 70-year-old with progressive dementia shows neurofibrillary tangles (NFTs) and senile plaques. NFTs in Alzheimer disease are composed primarily of:
- A Hyperphosphorylated tau forming paired helical filaments (PHFs) ✓
- B Alpha-synuclein filaments in Lewy body configuration
- C TDP-43 aggregates in ubiquitinated inclusions
- D Amyloid-beta fibrils in an intraneuronal distribution
Explanation
Neurofibrillary tangles (NFTs) in Alzheimer disease are composed of hyperphosphorylated tau protein that has dissociated from microtubules (where tau normally stabilizes tubulin polymerization) and aggregated into paired helical filaments (PHFs). Phosphorylation at specific serine/threonine residues (Ser202/Thr205 — AT8 epitope; Ser396/Ser404 — PHF-1 epitope) reduces tau's microtubule affinity. PHFs aggregate further into straight filaments and then NFTs, which are visualized by silver stains and tau IHC. Alpha-synuclein forms Lewy bodies (Parkinson disease, DLB); TDP-43 forms ubiquitinated inclusions in ALS/FTLD-TDP; amyloid-beta forms extracellular senile plaques, not NFTs.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.