Which statement best describes how tafamidis affects transthyretin tetramers?

• A. It destabilizes tetramers
• B. It stabilizes tetramers and reduces dissociation
• C. It promotes monomer aggregation
• D. It increases fibril formation

Answer: (B)

Tafamidis works by stabilizing the transthyretin tetramer, which keeps the protein from falling apart into monomers that can misfold and aggregate into amyloid fibrils. In healthy conditions, transthyretin forms a stable tetramer, but when the tetramer dissociates, the resulting monomers are prone to misfolding and assembling into amyloid deposits that cause disease. Tafamidis binds specifically to the thyroxine-binding sites on the tetramer, increasing the kinetic stability and strongly reducing dissociation. By preserving the tetramer, it lowers the formation of the pathogenic monomer and subsequent fibrils, slowing disease progression. It does not destabilize the tetramer, promote monomer aggregation, or increase fibril formation.