Pharmacology Presentation Drugs Practice Test

In ATTR, the problem starts with transthyretin becoming unstable due to mutations. This destabilizes the normal tetramer, causing it to fall apart into misfolded monomers. Those monomers can aggregate into insoluble amyloid fibrils that deposit in the heart tissue, particularly in the walls of the ventricles. As these deposits accumulate, the myocardium becomes infiltrated and stiff, leading to diastolic dysfunction and a restrictive form of cardiomyopathy. The disease mechanism is driven by abnormal protein folding and extracellular deposition, not by simply making more transthyretin or by autoimmune destruction.